Proof-of-concept recall-by-genotype study of extremely low and high Alzheimer's polygenic risk reveals autobiographical deficits and cingulate cortex correlates.

ABSTRACT:

Background

Genome-wide association studies demonstrate that Alzheimer's disease (AD) has a highly polygenic architecture, where thousands of independent genetic variants explain risk with high classification accuracy. This AD polygenic risk score (AD-PRS) has been previously linked to preclinical cognitive and neuroimaging features observed in asymptomatic individuals. However, shared variance between AD-PRS and neurocognitive features are small, suggesting limited preclinical utility.

Methods

Here, we recruited sixteen clinically asymptomatic individuals (mean age 67; range 58-76) with either extremely low / high AD-PRS (defined as at least 2 standard deviations from the wider sample mean (N = 4504; N _EFFECTIVE = 90)) with comparable age sex and education level.

SUBMITTER: Lancaster T 

PROVIDER: S-EPMC10714651 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature