Alzheimer's disease heterogeneity explained by polygenic risk scores derived from brain transcriptomic profiles.

ABSTRACT:

Introduction

Alzheimer's disease (AD) is heterogeneous, both clinically and neuropathologically. We investigated whether polygenic risk scores (PRSs) integrated with transcriptome profiles from AD brains can explain AD clinical heterogeneity.

Methods

We conducted co-expression network analysis and identified gene sets (modules) that were preserved in three AD transcriptome datasets and associated with AD-related neuropathological traits including neuritic plaques (NPs) and neurofibrillary tangles (NFTs). We computed the module-based PRSs (mbPRSs) for each module and tested associations with mbPRSs for cognitive test scores, cognitively defined AD subgroups, and brain imaging data.

Results

Of the modules significantly associated with NPs and/or NFTs, the mbPRSs from tw

SUBMITTER: Chung J 

PROVIDER: S-EPMC10638468 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature