APOE ε2ε4 genotype in older adults is associated with risk of mild cognitive impairment (MCI), cognitive decline, and a greater burden of Alzheimer disease (AD) pathology, especially β-amyloid, according to a recent study. Researchers used data from 2,151 older adults who were free of dementia at baseline and underwent structured annual clinical evaluation in a longitudinal study for incident AD and MCI, and cognitive decline. Postmortem examination in decedents documented pathologic AD and quantified β-amyloid and neurofibrillary tangles. Participants were stratified into 4 groups based on APOE genotyping: ε2ε4, ε4 (ε4ε4, ε4ε3), ε2 (ε2ε2, ε2ε3), with ε3ε3 carriers serving as the reference group. They found:

• Of total participants, ε2ε4 accounted for 2.1%, ε3/4 and 4/4 21.8%, ε2/3 and 2/2 14.0%, and ε3ε3 62.1%.
• There was no difference in the risk of AD for ε2ε4 compared to ε3ε3.
• In cases without cognitive impairment at baseline, ε2ε4 carriers had an increased risk of incident MCI and a faster rate of cognitive decline compared to ε3ε3 carriers.
• In decedents (n=1,100), ε2ε4 showed a 3-fold increased odds of pathologic AD and a higher β-amyloid load than ε3ε3.