The APOEε2 allele is associated with a milder Alzheimer disease (AD) pathology and less severe antemortem cognitive impairment compared to APOEε3 and ε4 alleles, suggesting a relative neuroprotective effect of APOEε2 in AD, according to an analysis of individuals from the National Alzheimer’s Coordinating Center autopsy cohort.
Investigators used multivariate models to examine the associations between APOE alleles and AD neuropathological changes, and found, compared to APOEε3:
• APOEε2 is associated with lower Braak neurofibrillary tangle (NFT) stages and possibly fewer neuritic plaques, but has no direct effect on cerebral amyloid angiopathy severity.
• APOEε4 is associated with more neuritic plaques and CAA, but has no independent effect on Braak NFT stage.
Citation: Serrano-Pozo A, Qian J, Monsell SE, Betensky RA, Hyman BT. APOEε2 is associated with milder clinical and pathological Alzheimer disease. Ann Neurol. 2015;77(6):917-929. doi:10.1002/ana.24369.