Association of Plasma Amylin Concentration With Alzheimer Disease and Brain Structure in Older Adults

Importance Preclinical studies suggest that amylin has a U-shaped dose-response association with risk of Alzheimer disease (AD). The association of plasma amylin with AD in humans is unknown. Objectives To measure amylin concentration in plasma by using enzyme-linked immunosorbent assay and to study the association between plasma amylin, incidence of AD, and brain structure in humans. Design, Setting, and Participants This cohort study used data from the Framingham Heart Study offspring cohort from 1998 to 2015. Using a Monte Carlo approach, participants were divided into 3 plasma amylin concentration groups: (1) low ( Exposures Baseline plasma amylin concentrations at examination 7. Main Outcomes and Measures Incidence of dementia or AD and brain volumetric measures from structural magnetic resonance imaging data. Results From the Framingham Heart Study offspring cohort, 3061 participants (mean [SD] age at baseline, 61.0 [9.5] years; 1653 [54.0%] women) who had plasma amylin measurements, dementia incidence, and brain volume measurements on record were included in this study. The distribution of plasma amylin concentrations was highly skewed (median [interquartile range], 7.5 [4.6-18.9] pmol/L; mean [SD], 302.3 [1941.0] pmol/L; range, 0.03-44 623.7 pmol/L). Compared with the low plasma amylin concentration group, the high plasma amylin concentration group had a lower rate of AD incidence (2.3% vs 5.6%;P = .04), but the extremely high plasma amylin concentration group had a higher rate of AD incidence (14.3%;P  Conclusions and Relevance This study found that plasma amylin concentration was associated with AD incidence and brain structure with a U-shaped pattern. These findings are consistent with preclinical findings that suggest amylin is a neuropeptide that is physiological; however, at extremely high concentrations, it may lead to amylin aggregation and therefore may be a risk factor for AD.