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Association of plasma amyloid β with risk of dementia

The prospective Three-City Study

From the Inserm U744 (J.-C.L., F.R., N.F., P.A.), Institut Pasteur de Lille; University of Lille 2 (J.-C.L., S.S.-M., F.R., L.B., P.A.); Inserm U837 (S.S.-M., L.B.), Lille; Service de Neurologie (O.R.), Centre Hospitalier Universitaire, Hôpital Général, Dijon; Inserm U888 (C.B.), University of Montpellier 1; Inserm U593 (J.-F.D.), Victor Segalen University, Bordeaux; and Inserm U708 (A.A., L.B.), Paris, France.

Address correspondence and reprint requests to Dr. Jean-Charles Lambert, Unité INSERM 744, Institut Pasteur de Lille, BP 245, 1, rue du professeur Calmette, F-59019 Lille cédex, France jean-charles.lambert{at}pasteur-lille.fr

Objective: Several lines of evidence indicate that a decrease in the CSF concentration of amyloid β₄₂ (Aβ₄₂) is a potential biomarker for incident Alzheimer disease. In contrast, studies on plasma Aβ_1–40 and Aβ_1–42 peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma Aβ_1–40 and Aβ_1–42 peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated Aβ (Aβ_n-40 and Aβ_n-42) and the risk of dementia.

Methods: During a subsequent 4-year follow-up period, 257 individuals presented incident dementia from 8,414 participants, and a subcohort of 1,185 individuals without dementia was drawn as a control cohort. Plasma levels of Aβ_1–40, Aβ_1–42, Aβ_n-40, and Aβ_n-42 were measured using an xMAP-based assay technology. The association between plasma Aβ peptide levels and the risk of dementia was assessed using Cox proportional hazard models.

Results: Of the various Aβ variables analyzed, the Aβ_1–42/Aβ_1–40 and Aβ_n-42/Aβ_n-40 ratios presented the strongest association with the risk of dementia: people with a high Aβ_1–42/Aβ_1–40 or Aβ_n-42/Aβ_n-40 ratio had a lower risk of developing dementia. These associations were restricted to individuals diagnosed at 2 years of follow-up and the Aβ_n-42/Aβ_n-40 ratio was mainly associated with the risk of mixed/vascular dementia.

Conclusion: Plasma Aβ peptide concentrations and Aβ_1–42/Aβ_1–40 and Aβ_n-42/Aβ_n-40 ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia.

Abbreviations: Aβ = amyloid β; AD = Alzheimer disease; BMI = body mass index; CI = confidence interval; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th edition; HDL = high-density lipoprotein; HR = hazard ratio; INSERM = Institut National de la Santé et de la Recherche Médicale; MCI = mild cognitive impairment; 3C = Three-City.

Supplemental data at www.neurology.org

Funding information is provided at the end of the article.

Disclosure: The authors report no disclosures.

Received January 27, 2009. Accepted in final form June 22, 2009.