Share

August 02, 2016; 87 (5) Article

Polygenic risk of Alzheimer disease is associated with early- and late-life processes

Elizabeth C. Mormino, Reisa A. Sperling, Avram J. Holmes, Randy L. Buckner, Philip L. De Jager, Jordan W. Smoller, Mert R. Sabuncu, For the Alzheimer's Disease Neuroimaging Initiative
First published July 6, 2016, DOI: https://doi.org/10.1212/WNL.0000000000002922
Full PDF
Citation
Permissions

Make Comment

See Comments

Downloads
733

Share

Article Information

vol. 87 no. 5 481-488
DOI: 
https://doi.org/10.1212/WNL.0000000000002922
PubMed: 
27385740
Published By: 
Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology
Print ISSN: 
0028-3878
Online ISSN: 
1526-632X
History: 
  • Received December 24, 2015
  • Accepted in final form April 22, 2016
  • First Published July 6, 2016.

Article Versions

Copyright & Usage: 
© 2016 American Academy of Neurology

Author Disclosures

    1. Elizabeth C. Mormino, PhD,
    2. Reisa A. Sperling, MD,
    3. Avram J. Holmes, PhD,
    4. Randy L. Buckner, PhD,
    5. Philip L. De Jager, MD, PhD,
    6. Jordan W. Smoller, MD, ScD,
    7. Mert R. Sabuncu, PhD;
    8. For the Alzheimer's Disease Neuroimaging Initiative
  1. Elizabeth C. Mormino, PhD,
    2. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. Funding Source: NIH/NIA Grant number: F32AG044054 Role: PI Years: 2/2015-current Funding Source: NIH/NIA Grant number: P01AG036694 Role: Co-investigator Years: 2/2015-current

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  2. Reisa A. Sperling, MD,
    3. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. 1)Commercial-Genentech travel 2)Not for Profit-Foundation for NIH- travel 3)Commercial- Otsuka Pharmaceuticals 4)Commercial- Lundbeck

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Personal: 1) Abbvie, commercial 2) Biogen, commercial 3) Genentech, commercial 4) Bracket, commercial 5)Roche, commercial 6) Sanofi, commercial 7) Lundbeck, commercial 8)Avid, commercial 9)Isis Pharmaceuticals, commercial 10)Otsuka Pharmaceuticals, commercial Spouse: 1)Lundbeck, commercial 2) Piramal Healthcare, commercial, 3) Siemens, commercial 4) Novartis

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Janssen- investigator-initiated imaging study, 2012-2014. Eli Lilly- clinical trial support 2014-present

    Research Support, Government Entities:

    1. 1) National Institute on Aging R01AG027435, Principal investigator, 2006-2017; 2) National Institute on Aging P01AG036694, principal investigator, 2010-2015; 3) National Institute on Aging P50AG005134, 2009-2014, Project leader; 4) National Institute on Aging U19 AG10483, Project Leader A4 trial, 2012-2017.

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. American Health Assistance Foundation, principal investigator, 2010-2014. Alzheimer's Association, co-principal investigator, 2012- 2014.

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  3. Avram J. Holmes, PhD,
    4. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIMH, K01MH099232, PI: Holmes, 2013-2018

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Brain & Behavior Research Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  4. Randy L. Buckner, PhD,
    5. Scientific Advisory Boards:

    1. paid consultant for Pfizer Scientific advisory board. 6 years.

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. Pfizer

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. R01 MH101486 (Smoller & Buckner) 09/16/13-06/30/17 0.83 cal NIH/NIMH $397,358 Neural and Genetic Basis of Negative Valance Traits The goal of this project is to define and validate a brain-based index of anxiety- and depression-related symptoms in order to provide novel insights into the biology of anxiety and depressive disorders, which may lead to biomarkers that can improve the diagnosis and targeted treatment of these conditions. Role: Co-Principle Investigator P01 AG036694 (Sperling) 07/15/10-06/30/15 1.20 cal NIH/NIA $117,1855 Impact of Amyloid on the Aging Brain The overall goals of the Program Project application are to elucidate the biological and clinical significance of amyloid deposition in clinically normal older individuals and to determine age-related functional and cognitive change in the absence of amyloid. Role: Principle Investigator of Project 1 R01 HD067744 (Valera) ??????????????????????????? 09/01/11-06/30/16 ?????????????? 0.12 cal NIH/NICHD ??????????????????????????????????????????????????????????? $280,421 The Role of Corticocerebellar Pathophysiology in Adult ADHD The long term objective of this proposal is to increase our understanding of the pathophysiology of attention deficit/hyperactivity disorder (ADHD) by furthering our knowledge regarding how the cerebellum and corticocerebellar circuits contribute to perceptual and motor timing abnormalities in ADHD. Role: Co-Investigator R01 AG046396 (Johnson) 01/01/14-12/31/18 0.12 cal NIH/NIA $499,107 Disentangling the contribution of tau to aging and AD The overall goal of this research is to determine the relationship of PET measures of PHF tau to Aβ deposition, brain structure and function, and cognition along the trajectories of aging and AD. Role: Co-Investigator P50 MH106435 (Haber) 04/1/15-03/31/20 3.00 cal NIH/NIMH $186,447 (Proj 3) / $84,193 (Core C) Neurcircuitry of OCD: Effects of Neuromodulation The overall goals of this Conte Center are to explore the circuitry of OCD in humans and develop methods for productively modulating that circuitry to alleviate symptoms. Project 3 seeks to develop methods to image networks at the level of individual subjects. Core C supports data management of neuroimaging across the Center. Role: Principle Investigator of Project 3 and Core C

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. NONE

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  5. Philip L. De Jager, MD, PhD,
    6. Scientific Advisory Boards:

    1. 1. TEVA Neuroscience, member of advisory board 2. Genzyme/Sanofi, member of advisory board

    Gifts:

    1. NONE

    Funding for travel or speaker honoraria:

    1. Biogen IDEC: speaker honoraria Source Healthcare Analytics Pfizer Inc: speaker honoraria TEVA: speaker honoraria

    Editorial Boards:

    1. Journal of Neuroimmunology - member of the Editorial Board Neuroepigenetics - associate editor Multiple Sclerosis journal - member of the Editorial Board

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. Biogen IDEC: research grant GSK: research grant Vertex: research grant Genzyme/Sanofi: research grant

    Research Support, Government Entities:

    1. NONE

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. National MS Society PI, 2008: JF2138A1

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  6. Jordan W. Smoller, MD, ScD,
    7. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH Grants: R01 MH085542 09/30/08 - 11/30/14 Role: Principal Investigator R01 MH081130 05/19/08 - 05/31/14 Role: Subcontract Investigator U01 MH087981 07/01/11 - 06/30/15 Role: Subcontract PI U01 MH09443201 05/10/12 - 03/31/16 Role: Co-Investigator R01 MH092380-01A1 09/10/12 - 07/31/16 Role: Co-Investigator R01 MH078829 03/01/12 ? 02/28/17 Role: Subcontract PI K24 MH094614 05/07/12 - 04/30/17 Role: Principal Investigator R01 MH101486 09/16/13 - 06/30/17 Role: Principal Investigator R01 MH101425 08/01/13 - 04/30/18 Role: Co-Investigator UL1 TR001102 09/26/13 - 04/30/18 Role: Co-Investigator R56 HD085284 09/01/15 - 08/31/16 Role: Principal Investigator R01 MH106547-01 04/01/15 ? 03/31/18 Role: Principal Investigator U01 HG008685 09/01/15 ? 05/31/19 Role: Multi-PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. Tommy Fuss Fund Dearest Lloyd Foundation

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  7. Mert R. Sabuncu, PhD;
    8. Scientific Advisory Boards:

    1. NONE

    Gifts:

    1. NONE

    Funding for Travel or Speaker Honoraria:

    1. NONE

    Editorial Boards:

    1. NONE

    Patents:

    1. NONE

    Publishing Royalties:

    1. NONE

    Employment, Commercial Entity:

    1. NONE

    Consultancies:

    1. NONE

    Speakers' Bureaus:

    1. NONE

    Other Activities:

    1. NONE

    Clinical Procedures or Imaging Studies:

    1. NONE

    Research Support, Commercial Entities:

    1. NONE

    Research Support, Government Entities:

    1. NIH, K25-EB013649, 2011-2016, PI NIH, R41-AG052246, 2015-2016, Co-PI

    Research Support, Academic Entities:

    1. NONE

    Research Support, Foundations and Societies:

    1. BrightFocus Foundation - Alzheimer's disease pilot grant (A2012333)

    Stock/Stock Options/Board of Directors Compensation:

    1. NONE

    License Fee Payments, Technology or Inventions:

    1. NONE

    Royalty Payments, Technology or Inventions:

    1. NONE

    Stock/Stock Options, Research Sponsor:

    1. NONE

    Stock/Stock Options, Medical Equipment & Materials:

    1. NONE

    Legal Proceedings:

    1. NONE

  8. For the Alzheimer's Disease Neuroimaging Initiative
    1. From the Departments of Neurology (E.C.M., R.A.S.) and Radiology (R.A.S.), Massachusetts General Hospital, Harvard Medical School, Charlestown; Center for Alzheimer Research and Treatment, Department of Neurology (R.A.S.), and Program in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry (P.L.D.), Brigham and Women's Hospital, Harvard Medical School (P.L.D.), Boston, MA; Department of Psychology (A.J.H.), Yale University, New Haven, CT; Department of Psychiatry (A.J.H.), Massachusetts General Hospital, Harvard Medical School, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A.J.H.) and Psychiatric and Neurodevelopmental Genetics Unit, Center for Human Genetic Research (J.W.S.), Massachusetts General Hospital, Boston; Department of Psychology and Center for Brain Science (R.L.B.), Harvard University, Cambridge; Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology (R.L.B., M.R.S.), Massachusetts General Hospital, Charlestown; Program in Medical and Population Genetics (P.L.D.), Broad Institute; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard (J.W.S.); and Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge.
    1. Correspondence to Dr. Mormino: bmormino{at}nmr.mgh.harvard.edu
    View Full Text

    Article usage

    Article usage: July 2016 to April 2023

    AbstractFullPdfSource
    Jul 201649863181Highwire
    Aug 201623782865Highwire
    Sep 20164981718Highwire
    Oct 2016451109Highwire
    Nov 2016373148Highwire
    Dec 2016305114Highwire
    Jan 201726599Highwire
    Feb 20172101011Highwire
    Mar 2017162911Highwire
    Apr 201712254Highwire
    May 2017138109Highwire
    Jun 201712925Highwire
    Jul 201710133Highwire
    Aug 20178846Highwire
    Aug 2017232918pmc
    Sep 20179625Highwire
    Sep 2017112634pmc
    Oct 20179365Highwire
    Oct 2017132930pmc
    Nov 20177842Highwire
    Nov 2017203436pmc
    Dec 201778123Highwire
    Jan 20187932Highwire
    Feb 20185772Highwire
    Mar 201875104Highwire
    Apr 20188913Highwire
    Apr 201863338pmc
    May 20189065Highwire
    Jun 20188410Highwire
    Jun 201883136pmc
    Jul 20189521Highwire
    Aug 20185697Highwire
    Aug 2018103032pmc
    Sep 20186034Highwire
    Oct 20186856Highwire
    Nov 20187140Highwire
    Dec 20187200Highwire
    Jan 20196335Highwire
    Feb 20197428Highwire
    Mar 20197323Highwire
    Apr 20198368Highwire
    May 20196122Highwire
    Jun 20196023Highwire
    Jul 201942153Highwire
    Aug 20194681Highwire
    Sep 20194211Highwire
    Oct 20195645Highwire
    Nov 20198620Highwire
    Dec 20193901Highwire
    Jan 20207332Highwire
    Feb 20208044Highwire
    Mar 20207992Highwire
    Apr 20204331Highwire
    May 20204501Highwire
    Jun 20206022Highwire
    Jul 20206810Highwire
    Aug 20204874Highwire
    Sep 20207120Highwire
    Oct 20206221Highwire
    Nov 20208221Highwire
    Dec 20207312Highwire
    Jan 20216201Highwire
    Feb 20218112Highwire
    Mar 20219692Highwire
    Apr 202110123Highwire
    May 20216647Highwire
    Jun 20218142Highwire
    Jul 20216432Highwire
    Aug 20216322Highwire
    Sep 20219021Highwire
    Oct 20217942Highwire
    Nov 20217622Highwire
    Dec 202112201Highwire
    Jan 202213852Highwire
    Feb 20228844Highwire
    Mar 202215222Highwire
    Apr 20229652Highwire
    May 202210052Highwire
    Jun 20228120Highwire
    Jul 20227922Highwire
    Aug 20228110Highwire
    Sep 20226853Highwire
    Oct 202212730Highwire
    Nov 20229683Highwire
    Dec 202210142Highwire
    Jan 202310130Highwire
    Feb 20239342Highwire
    Mar 20237652Highwire
    Apr 202310754Highwire

    Cited By...

    Letters: Rapid online correspondence

    No comments have been published for this article.
    Comment

    REQUIREMENTS

    You must ensure that your Disclosures have been updated within the previous six months. Please go to our Submission Site to add or update your Disclosure information.

    Your co-authors must send a completed Publishing Agreement Form to Neurology Staff (not necessary for the lead/corresponding author as the form below will suffice) before you upload your comment.

    If you are responding to a comment that was written about an article you originally authored:
    You (and co-authors) do not need to fill out forms or check disclosures as author forms are still valid
    and apply to letter.

    Submission specifications:

    • Submissions must be < 200 words with < 5 references. Reference 1 must be the article on which you are commenting.
    • Submissions should not have more than 5 authors. (Exception: original author replies can include all original authors of the article)
    • Submit only on articles published within 6 months of issue date.
    • Do not be redundant. Read any comments already posted on the article prior to submission.
    • Submitted comments are subject to editing and editor review prior to posting.

    More guidelines and information on Disputes & Debates

    Compose Comment

    More information about text formats

    Plain text

    • No HTML tags allowed.
    • Web page addresses and e-mail addresses turn into links automatically.
    • Lines and paragraphs break automatically.
    Author Information
    NOTE: The first author must also be the corresponding author of the comment.
    First or given name, e.g. 'Peter'.
    Your last, or family, name, e.g. 'MacMoody'.
    Your email address, e.g. higgs-boson@gmail.com
    Your role and/or occupation, e.g. 'Orthopedic Surgeon'.
    Your organization or institution (if applicable), e.g. 'Royal Free Hospital'.
    Publishing Agreement
    NOTE: All authors, besides the first/corresponding author, must complete a separate Publishing Agreement Form and provide via email to the editorial office before comments can be posted.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.

    Vertical Tabs

    You May Also be Interested in

    Back to top
    Advertisement

    Topics Discussed

    Alert Me

    Recommended articles