Association of plasma β-amyloid with MRI markers of structural brain aging the 3-City Dijon study

Cerebral β-amyloid (Aβ) deposition and atrophy are central features of Alzheimer disease. Studies of Alzheimer disease biomarkers have largely focused on Aβ in cerebrospinal fluid (CSF), and there is uncertainty as to what plasma Aβ may be a marker. We examined the association of Aβ levels in the plasma with magnetic resonance imaging (MRI)-markers of brain aging, including longitudinal changes in global and regional brain volumes, in dementia-free persons. We studied 1530 participants of the Three-City-Dijon cohort, aged 65-80 years. Plasma Aβ measurement and magnetic resonance imaging were performed at baseline and after a 4-year follow up. Total brain, gray matter, and hippocampal volume were estimated using voxel-based morphometry, and annualized change in brain volumes was calculated. Increased plasma Aβ1-40 was associated with lower baseline hippocampal volume. Although baseline plasma Aβ levels were not associated with longitudinal change in brain volumes, consistently high plasma Aβ1-40 levels were associated with faster total brain atrophy and consistently low plasma Aβ1-42/Aβ1-40 ratio, with increased total brain atrophy and gray matter atrophy. In dementia-free older adults, high plasma Aβ1-40 and low plasma Aβ1-42/Aβ1-40 ratio were associated with smaller hippocampal volume and accelerated global and regional brain atrophy respectively.