Iacono · Oncotarget 2015 · Clinicopathological case-comparison study · n=523

APOε2 and education in cognitively normal older subjects with high levels of AD pathology at autopsy: findings from the Nun Study.

Cited 18 times in the scientific literature.

Level 4 - case-series / case-control

Cross-sectional clinicopathological case-comparison study within an autopsy cohort.

PubMed 26101858 · doi:10.18632/oncotarget.4118 · record verified 2026-08-30

What was done

Researchers screened 523 autopsied brains from the longitudinal Nun Study to investigate whether APOE alleles and educational attainment differentiate asymptomatic Alzheimer's disease (ASYMAD; intact antemortem cognition despite substantial postmortem amyloid-beta and tau pathology) from mild cognitive impairment (MCI) and definite AD with comparable neuropathology.

What was found

APOε2 allele frequency was significantly higher in the ASYMAD group (19.2%) compared to MCI (0%) and AD (4.7%) (p < 0.001). Educational attainment was also significantly higher in ASYMAD individuals compared to both MCI and AD groups (p < 0.05).

Why it matters

The findings indicate that carrying the APOε2 allele and achieving higher education may confer cognitive resilience, delaying or preventing clinical cognitive impairment despite the accumulation of heavy Alzheimer neuropathology.

Limits

The population was drawn entirely from the Nun Study (Catholic sisters), which limits generalizability to broader demographic and socioeconomic groups. The abstract does not report the specific sample size broken down per subgroup (ASYMAD, MCI, AD) out of the 523 screened, nor does it report precise metrics, means, or effect sizes for the education comparison beyond the p-value.

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