February 12, 2019; 92 (7) Medical Hypothesis
Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases
Alberto J. Espay, View ORCID ProfileJoaquin A. Vizcarra, Luca Marsili, Anthony E. Lang, David K. Simon, Aristide Merola, Keith A. Josephs, Alfonso Fasano, Francesca Morgante, Rodolfo Savica, J. Timothy Greenamyre, Franca Cambi, Tritia R. Yamasaki, Caroline M. Tanner, Ziv Gan-Or, Irene Litvan, Ignacio F. Mata, Cyrus P. Zabetian, Patrik Brundin, Hubert H. Fernandez, David G. Standaert, Marcelo A. Kauffman, Michael A. Schwarzschild, S. Pablo Sardi, Todd Sherer, George Perry, James B. Leverenz
First published February 11, 2019, DOI: https://doi.org/10.1212/WNL.0000000000006926
Alberto J. Espay
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Joaquin A. Vizcarra
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Luca Marsili
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Anthony E. Lang
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
David K. Simon
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Aristide Merola
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Keith A. Josephs
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Alfonso Fasano
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Francesca Morgante
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Rodolfo Savica
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
J. Timothy Greenamyre
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Franca Cambi
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Tritia R. Yamasaki
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Caroline M. Tanner
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Ziv Gan-Or
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Irene Litvan
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Ignacio F. Mata
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Cyrus P. Zabetian
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Patrik Brundin
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Hubert H. Fernandez
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
David G. Standaert
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Marcelo A. Kauffman
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Michael A. Schwarzschild
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
S. Pablo Sardi
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Todd Sherer
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
George Perry
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
James B. Leverenz
From the UC Gardner Neuroscience Institute and Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., J.A.V., L.M., A.M.), Department of Neurology, University of Cincinnati, OH; Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic (A.E.L., A.F.), Toronto Western Hospital, University of Toronto; Krembil Research Institute (A.E.L., A.F.), Toronto, Canada; Parkinson's Disease and Movement Disorders Center (D.K.S.), Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; College of Medicine (K.A.J.), Mayo Clinic, Rochester, MN; Institute of Molecular and Clinical Sciences (F.M.), St George's University of London, UK; Division of Movement Disorders (R.S.), Department of Neurology and Department of Health Science Research, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology and the Pittsburgh Institute for Neurodegenerative Diseases (J.T.G., F.C.), University of Pittsburgh, PA; Department of Neurology (T.R.Y.), University of Kentucky, Lexington; Parkinson's Disease Research, Education and Clinical Center (C.M.T.), Neurology, San Francisco Veterans Affairs Medical Center; Department of Neurology (C.M.T.), University of California–San Francisco; Department of Neurology & Neurosurgery, Montreal Neurological Institute, and Department of Human Genetics (Z.G.-O.), McGill University, Canada; Parkinson & Other Movement Disorders Center UC San Diego (I.L.), Department of Neurosciences, Altman Clinical Translational Research Institute, La Jolla, CA; VA Puget Sound Health Care System and Department of Neurology (I.F.M., CP.Z.), University of Washington, Seattle; Department of Neurology (I.F.M.), University of Washington School of Medicine, Seattle; Center for Neurodegenerative Science (P.B.), Van Andel Research Institute, Grand Rapids, MI; Center for Neurological Restoration (H.H.F.) and Lou Ruvo Center for Brain Health, Neurological Institute (J.B.L.), Cleveland Clinic, OH; Department of Neurology (D.G.S.), University of Alabama at Birmingham; Consultorio y Laboratorio de Neurogenética (M.A.K.), Centro Universitario de Neurología “José María Ramos Mejía” y División Neurología, Hospital JM Ramos Mejía, Facultad de Medicina, UBA; Programa de Medicina de Precision y Genomica Clinica (M.A.K.), Instituto de Investigaciones en Medicina Traslacional, Facultad de Ciencias Biomédicas, Universidad Austral-CONICET, Buenos Aires, Argentina; Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Division of Neuroscience (S.P.S.), Sanofi-Genzyme, Framingham, MA; Michael J. Fox Foundation for Parkinson's Research (T.S.), New York, NY; and College of Sciences (G.P.), University of Texas at San Antonio.
Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases
Alberto J. Espay, Joaquin A. Vizcarra, Luca Marsili, Anthony E. Lang, David K. Simon, Aristide Merola, Keith A. Josephs, Alfonso Fasano, Francesca Morgante, Rodolfo Savica, J. Timothy Greenamyre, Franca Cambi, Tritia R. Yamasaki, Caroline M. Tanner, Ziv Gan-Or, Irene Litvan, Ignacio F. Mata, Cyrus P. Zabetian, Patrik Brundin, Hubert H. Fernandez, David G. Standaert, Marcelo A. Kauffman, Michael A. Schwarzschild, S. Pablo Sardi, Todd Sherer, George Perry, James B. Leverenz
Neurology Feb 2019, 92 (7) 329-337; DOI: 10.1212/WNL.0000000000006926
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Abstract
The gold standard for a definitive diagnosis of Parkinson disease (PD) is the pathologic finding of aggregated α-synuclein into Lewy bodies and for Alzheimer disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinicopathologic-based nosology is the assumption that pathologic protein aggregation at autopsy reflects pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated α-synuclein in SNCA gene multiplication or aggregated β-amyloid in APP mutations), their near universality at postmortem in sporadic PD and AD suggests they may alternatively represent common outcomes from upstream mechanisms or compensatory responses to cellular stress in order to delay cell death. These 3 conceptual frameworks of protein aggregation (pathogenic, epiphenomenon, protective) are difficult to resolve because of the inability to probe brain tissue in real time. Whereas animal models, in which neither PD nor AD occur in natural states, consistently support a pathogenic role of protein aggregation, indirect evidence from human studies does not. We hypothesize that (1) current biomarkers of protein aggregates may be relevant to common pathology but not to subgroup pathogenesis and (2) disease-modifying treatments targeting oligomers or fibrils might be futile or deleterious because these proteins are epiphenomena or protective in the human brain under molecular stress. Future precision medicine efforts for molecular targeting of neurodegenerative diseases may require analyses not anchored on current clinicopathologic criteria but instead on biological signals generated from large deeply phenotyped aging populations or from smaller but well-defined genetic–molecular cohorts.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- DLB=
- dementia with Lewy bodies;
- PD=
- Parkinson disease
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received July 6, 2018.
- Accepted in final form December 14, 2018.
- © 2019 American Academy of Neurology
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Letters: Rapid online correspondence
- Author response to Dr. Nelson: Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases
- Alberto J. Espay, Neurologist, University of Cincinnati
- Joaquin A. Vizcarra, Neurologist, University of Cincinnati
- Luca Marsili, Neurologist, University of Cincinnati
- Anthony E. Lang, Neurologist, University of Toronto
- S. Pablo Sardi, Neuroscientist, Sanofi Pharmaceuticals
- James B. Leverenz, Neurologist, Cleveland Clinic Foundation
Submitted March 22, 2019 - Reader response: Revisiting protein aggregation as pathogenic in sporadic Parkinson and Alzheimer diseases
- Peter T. Nelson, Neuropathologist, University of Kentucky
Submitted February 15, 2019
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