Decreased plasma β-amyloid in the Alzheimer's disease APP A673T variant carriers.

We investigated the association of Alzheimer's disease (AD)-related rare variants APP A673T and ABCA7 rs200538373-C with the levels of β-amyloid (Aβ) and parameters of metabolic and cardiovascular health in a population-based cohort of healthy middle-aged and elderly men. Carriers of protective APP A673T variant had, on average, 28% lower levels of Aβ40 and Aβ42 in plasma as compared to the controls and the carriers of ABCA7 rs200538373-C. This is the first report to show decreased Aβ levels in plasma in APP A673T carriers and thus provides evidence that lower Aβ levels throughout life may be protective against AD. Ann Neurol 2017;82:128-132.