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

Objective: Several lines of evidence indicate that a decrease in the CSF concentration of amyloid beta(42) (A beta(42)) is a potential biomarker for incident Alzheimer disease. In contrast, studies on plasma A beta(1-40) and A beta(1-42) peptide levels have yielded contradictory results. Here, we explored the links between incident dementia and plasma A beta(1-40) and A beta(1-42) peptide concentrations in the prospective, population-based Three-City (3C) Study. We also assessed the association between plasma concentrations of truncated A beta(A beta(n-40) and A beta(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 A beta(1-40), A beta(1-42), A beta(n-40), and A beta(n-42) were measured using an xMAP-based assay technology. The association between plasma A beta peptide levels and the risk of dementia was assessed using Cox proportional hazard models. Results: Of the various A beta variables analyzed, the A beta(1-42)/A beta(1-40) and A beta(n-42)/A beta(n-40) ratios presented the strongest association with the risk of dementia: people with a high A beta(1) (42)/A beta(1) (40) or A beta(n-42)/A beta(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 A beta(n-42)/A beta(n-40) ratio was mainly associated with the risk of mixed/vascular dementia. Conclusion: Plasma A beta peptide concentrations and A beta(1-42)/A beta(1-40) and A beta(n-42)/A beta(n-40) ratios may be useful markers to indicate individuals susceptible to short-term risk of dementia. Neurology (R) 2009;73: 847-853