APOE ɛ4, but not polygenic Alzheimer's disease risk, is related to longitudinal decrease in hippocampal brain activity in non-demented individuals.

ABSTRACT: The hippocampus is affected early in Alzheimer's disease (AD) and altered hippocampal functioning influences normal cognitive aging. Here, we used task-based functional MRI to assess if the APOE ɛ4 allele or a polygenic risk score (PRS) for AD was linked to longitudinal changes in memory-related hippocampal activation in normal aging (baseline age 50-95, n = 292; n = 182 at 4 years follow-up, subsequently non-demented for at least 2 years). Mixed-models were used to predict level and change in hippocampal activation by APOE ɛ4 status and PRS based on gene variants previously linked to AD at p ≤ 1, p < 0.05, or p < 5e-8 (excluding APOE). APOE ɛ4 and PRS_p<5e-8 significantly predicted AD risk in a larger sample from the same study population (n = 1542), while PRS_p≤1 pred

SUBMITTER: Haglin S 

PROVIDER: S-EPMC10209089 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature