APOE varepsilon2 and presymptomatic stage Alzheimer disease: how much is not enough?

摘要

Although its mechanism of action is still debated, the effect of APOE genotype on risk and age at onset of Alzheimer disease (AD) has been replicated many times. Because APOE sA increases AD risk, epsilon4 carriers have provided an unparalleled opportunity to study the metabolic, structural, pathologic, and cognitive changes that precede the symptomatic expression of mild cognitive impairment (MCI) and dementia and have led to the identification and characterization of presymptomatic stage AD. By contrast, APOE epsilon2 confers a reduced risk of AD, but is the least prevalent of the 3 common APOE alleles. Although epsilon2's protective effect has been considered for therapeutic purposes of primary prevention, surprisingly few studies have examined the epsilon2 effect on brain and cognitive aging.