| Popis: |
INTRODUCTIONAlzheimer’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.METHODSWe conducted co-expression analysis and identified gene-sets (modules) which were preserved in three AD transcriptome datasets and associated with AD-related neuropathological traits for neuritic plaques (NPs) or neurofibrillary tangles (NFTs). We computed the module-based PRS (mbPRS) for each module and tested associations for mbPRSs with cognitive test scores, cognitively-defined AD subgroups, and brain imaging data.RESULTSOf the modules significantly associated with NPs and/or NFTs, the mbPRSs from two modules (M6 and M9) showed distinct associations with language and visuospatial functioning as well as their matching AD-subgroups and brain atrophy at specific regions.DISCUSSIONOur findings demonstrate that polygenic profiling based on co-expressed gene-sets can explain heterogeneity in AD patients, enabling to genetically-informed patient stratification and precision medicine in AD. |
