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August 28, 2012; 79 (9) Articles

Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease

William T. Hu, David M. Holtzman, Anne M. Fagan, Leslie M. Shaw, Richard Perrin, Steven E. Arnold, Murray Grossman, Chengjie Xiong, Rebecca Craig-Schapiro, Christopher M. Clark, Eve Pickering, Max Kuhn, Yu Chen, Vivianna M. Van Deerlin, Leo McCluskey, Lauren Elman, Jason Karlawish, Alice Chen-Plotkin, Howard I. Hurtig, Andrew Siderowf, Frank Swenson, Virginia M.-Y. Lee, John C. Morris, John Q. Trojanowski, Holly Soares
First published August 1, 2012, DOI: https://doi.org/10.1212/WNL.0b013e318266fa70
William T. Hu
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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David M. Holtzman
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Anne M. Fagan
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Leslie M. Shaw
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Richard Perrin
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Steven E. Arnold
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Murray Grossman
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Chengjie Xiong
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Rebecca Craig-Schapiro
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Christopher M. Clark
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Eve Pickering
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Max Kuhn
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Yu Chen
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Vivianna M. Van Deerlin
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Leo McCluskey
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Lauren Elman
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Jason Karlawish
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Alice Chen-Plotkin
From the Department of Neurology (W.T.H., M.G., L.M., L.E., A.C.-P., H.I.H., A.S.), Center for Neurodegenerative Disease Research (W.T.H., L.M.S., V.M.V.D., A.C.-P., V.M.-Y.L., J.Q.T.), Departments of Psychiatry (S.E.A.) and Pathology and Laboratory Medicine (L.M.S., V.M.V.D., V.M.-Y.L., J.Q.T.), Institute on Aging (S.E.A., V.M.-Y.L., J.Q.T.), and Department of Medicine (J.K.), University of Pennsylvania School of Medicine, Philadelphia; Department of Neurology (D.M.H., A.M.F., R.C.-S., J.C.M.) and Knight Alzheimer's Disease Research Center (D.M.H., A.M.F., R.P., C.X., R.C.-S., J.C.M.), Washington University School of Medicine, St. Louis, MO; Department of Neurology (W.T.H.), Emory University School of Medicine, Atlanta, GA; Avid Pharmaceuticals (C.M.C.), Philadelphia, PA; Pfizer Global Research and Development (E.P., M.K., Y.C., F.S.), Groton, CT; and Bristol-Myers Squibb (H.S.), New London, CT.
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Howard I. Hurtig
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Citation
Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease
William T. Hu, David M. Holtzman, Anne M. Fagan, Leslie M. Shaw, Richard Perrin, Steven E. Arnold, Murray Grossman, Chengjie Xiong, Rebecca Craig-Schapiro, Christopher M. Clark, Eve Pickering, Max Kuhn, Yu Chen, Vivianna M. Van Deerlin, Leo McCluskey, Lauren Elman, Jason Karlawish, Alice Chen-Plotkin, Howard I. Hurtig, Andrew Siderowf, Frank Swenson, Virginia M.-Y. Lee, John C. Morris, John Q. Trojanowski, Holly Soares
Neurology Aug 2012, 79 (9) 897-905; DOI: 10.1212/WNL.0b013e318266fa70

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  • Plasma multianalyte profiling in mild cognitive impairment and Alzheimer disease - October 30, 2012
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Abstract

Objectives: While plasma biomarkers have been proposed to aid in the clinical diagnosis of Alzheimer disease (AD), few biomarkers have been validated in independent patient cohorts. Here we aim to determine plasma biomarkers associated with AD in 2 independent cohorts and validate the findings in the multicenter Alzheimer's Disease Neuroimaging Initiative (ADNI).

Methods: Using a targeted proteomic approach, we measured levels of 190 plasma proteins and peptides in 600 participants from 2 independent centers (University of Pennsylvania, Philadelphia; Washington University, St. Louis, MO), and identified 17 analytes associated with the diagnosis of very mild dementia/mild cognitive impairment (MCI) or AD. Four analytes (apoE, B-type natriuretic peptide, C-reactive protein, pancreatic polypeptide) were also found to be altered in clinical MCI/AD in the ADNI cohort (n = 566). Regression analysis showed CSF Aβ42 levels and t-tau/Aβ42 ratios to correlate with the number of APOE4 alleles and plasma levels of B-type natriuretic peptide and pancreatic polypeptide.

Conclusion: Four plasma analytes were consistently associated with the diagnosis of very mild dementia/MCI/AD in 3 independent clinical cohorts. These plasma biomarkers may predict underlying AD through their association with CSF AD biomarkers, and the association between plasma and CSF amyloid biomarkers needs to be confirmed in a prospective study.

GLOSSARY

Aβ42=
βamyloid 1–42;
AD=
Alzheimer disease;
ADNI=
Alzheimer's Disease Neuroimaging Initiative;
BNP=
B-type natriuretic peptide;
CDR=
Clinical Dementia Rating;
CRP=
C-reactive protein;
CV=
coefficient of variation;
IGF-BP2=
insulin growth factor binding protein 2;
IL=
interleukin;
IUT=
Intersection Union Test;
MCI=
mild cognitive impairment;
p-tau181=
tau phosphorylated at threonine 181;
Penn=
University of Pennsylvania;
RBM=
Rules-Based Medicine;
SAM=
significance analysis of microarrays;
t-tau=
total tau;
TARC=
Texas Alzheimer's Research Consortium;
WU=
Washington University

Footnotes

  • ↵† Deceased.

  • Coinvestigators are listed on the Neurology® Web site at www.neurology.org.

  • Additional corresponding authors: holtzman{at}neuro.wustl.edu, Les.Shaw{at}uphs.upenn.edu, trojanow{at}mail.med.upenn.edu, holly.soares{at}bms.com.

  • Study funding: Funding information is provided at the end of the article.

  • Editorial, page 846

  • Supplemental data at www.neurology.org

  • Received August 11, 2011.
  • Accepted March 8, 2012.
  • Copyright © 2012 by AAN Enterprises, Inc.
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Letters: Rapid online correspondence

  • Response to Dr. Bennett
    • William T Hu, Assistant Professor, Neurology, Emory Universitywthu@emory.edu
    • David Holtzman, St. Louis, MO; Leslie Shaw, Philadelphia, PA; John Trojanowski, Philadelphia, PA; Holly Soares, New London, CT
    Submitted August 30, 2012
  • Proteomics and Alzheimer Disease (AD)
    • David A. Bennett, Director and Professor of Neurological Sciences, Rush Alzheimer's Disease Center, Rush University Medical CenterDavid_A_Bennett@rush.edu
    • Chicago, IL
    Submitted August 28, 2012
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