Plasma amyloid-β and risk of Alzheimer's disease in the Framingham Heart Study

Vincent Chouraki, Alexa Beiser, Linda Younkin, Sarah Rosner Preis, Galit Weinstein, Oskar Hansson, Ingmar Skoog, Jean Charles Lambert, Rhoda Au, Lenore Launer, Philip A. Wolf, Steven Younkin, Sudha Seshadri

Research output: Contribution to journalArticlepeer-review


Background Plasma amyloid-β (Aβ) peptide levels have been examined as a low-cost accessible marker for risk of incident Alzheimer's disease (AD) and dementia, but results have varied between studies. We reassessed these associations in one of the largest, prospective, community-based studies to date. Methods A total of 2189 dementia-free, Framingham Study participants aged >60 years (mean age, 72 ± 8 years; 56% women) had plasma Aβ1-42 and Aβ1-40 measured and were followed prospectively (mean, 7.6 ± 3.0 years) for dementia/AD. Results Increased plasma Aβ1-42 levels were associated with lower risk of dementia (Aβ1-42: hazard ratio [HR] = 0.80 [0.71†0.90], P <.001; Aβ1-42-to-Aβ1-40 ratio: HR = 0.86 [0.76†0.98], P =.027) and AD (Aβ1-42: HR = 0.79 [0.69†0.90], P <.001; Aβ1-42-to-Aβ1-40 ratio: HR = 0.83 [0.72†0.96], P =.012). Conclusion Our results suggest that lower plasma Aβ levels are associated with risk of incident AD and dementia. They encourage further evaluation of plasma Aβ levels as a biomarker for risk of developing clinical AD and dementia.

Original languageEnglish
Pages (from-to)249-257.e1
JournalAlzheimer's and Dementia
Issue number3
StatePublished - 1 Mar 2015
Externally publishedYes

Bibliographical note

Funding Information:
Three-City Study: The Three-City (3C) Study was performed as part of a collaboration among the Institut National de la Santé et de la Recherche Médicale (INSERM), the Victor Segalen-Bordeaux II University, and Sanofi-Synthelabo. The Fondation pour la Recherche Médicale funded the preparation and initiation of the study. The 3C Study was also funded by the Caisse Nationale Maladie des Travailleurs Salariés , Direction Générale de la Santé , MGEN , Institut de la Longevité , Agence Francaise de Securité Sanitaire des Produits de Santé , the Aquitaine and Bourgogne Regional Councils , Fondation de France , and the joint French Ministry of Research / National Institute of Health and Medical Research “Cohortes et collections de données biologiques” program. Lille Génopole received an unconditional grant from Eisai . This work was additionally funded by the CNRS , the Nord Pas-de-Calais Regional Council , and the European Regional Development Fund , and grants from INSERM-DHOS-INCA (Project A08037ECS) and the European Community's cNEUPRO programme (contract LSHM-CT-2007-037950).

Funding Information:
Honolulu Asia Aging Study: This work was supported by the National Institutes of Health (National Institute on Aging contract NO1-AG-4-2149, cooperative agreements 5U01AG017155-09 and 5U01AG019349-08, and the Intramural Research Program of the National Institutes of Health and with resources at the Veterans Affairs Pacific Islands Health Care System).

Funding Information:
This work was supported by the dedication of the Framingham Heart Study participants.

Funding Information:
Framingham Heart Study: This work received support from the National Heart, Lung and Blood Institute 's Framingham Heart Study (contract no. N01-HC-25195) and grants from the National Institute of Neurological Disorders and Stroke ( NS17950 ) and the National Institute on Aging ( AG08122 , AG16495 , and AG033193 ).

Publisher Copyright:
© 2015 The Alzheimer's Association.


  • Alzheimer's disease
  • Aβ peptides
  • Epidemiology
  • Framingham
  • Heart
  • Incident
  • Incident dementia
  • Meta-analysis
  • Plasma biomarker
  • Study

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


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