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

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 Aβ_1-42 and Aβ_1-40 measured and were followed prospectively (mean, 7.6 ± 3.0 years) for dementia/AD. Results Increased plasma Aβ_1-42 levels were associated with lower risk of dementia (Aβ_1-42: hazard ratio [HR] = 0.80 [0.71†0.90], P <.001; Aβ_1-42-to-Aβ_1-40 ratio: HR = 0.86 [0.76†0.98], P =.027) and AD (Aβ_1-42: HR = 0.79 [0.69†0.90], P <.001; Aβ_1-42-to-Aβ_1-40 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.