Association of plasma amyloid   with risk of dementia: The prospective Three-City Study

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 Aβ1–40 and Aβ1–42 peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma Aβ1–40 and Aβ1–42 peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated Aβ (Aβn-40 and Aβn-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 Aβ1–40, Aβ1–42, Aβn-40, and Aβn-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 Aβ1–42/Aβ1–40 and Aβn-42/Aβn-40 ratios presented the strongest association with the risk of dementia: people with a high Aβ1–42/Aβ1–40 or Aβn-42/Aβn-40 ratio had a lower risk of developing dementia. These associations were restricted to individuals diagnosed at 2 years of follow-up and the Aβn-42/Aβn-40 ratio was mainly associated with the risk of mixed/vascular dementia. Conclusion: Plasma Aβ peptide concentrations and Aβ1–42/Aβ1–40 and Aβn-42/Aβn-40 ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia.