ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
Alzheimer's disease heterogeneity explained by polygenic risk scores derived from brain transcriptomic profiles.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 2 citations in OpenAlex.
- Cell-based polygenic risk scores predict clinical progression and prioritize network-based therapeutic targets in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Beyond Targeted Gene Panels: Whole-Exome Sequencing as a Strategic Platform for Precision Therapeutics in Alzheimer's Disease.Life (Basel, Switzerland) · 2026Review
- Neural network-enhanced investigation of ferroptosis and druggability in early-onset alzheimer's disease.Metabolic brain disease · 2026Article
- KetoFLEX 12/3 Diet and Cognitive Health: A Precision-Nutrition Perspective on Mechanisms, Emerging Evidence, and Future Directions.Nutrients · 2026Review
- Imaging Genomics Across Primate Species: Advancing Understanding of Neurological and Psychiatric Disorders.Neuroscience bulletin · 2026Review
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Integrating polygenic and transcriptional risk scores for detecting Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Blood-Brain Network-Based Polygenic Risk Scores Reveal Biomarker Signatures and the Progression of Alzheimer's Disease.Journal of clinical medicine · 2026Article
- An integrative neurogenomics workflow for precision medicine in neurodegenerative disorders.Frontiers in dementia · 2026Article
- Peripheral blood microarray-based transcriptomic and epigenetic analyses identify immune, inflammation, and metabolic dysregulation in Alzheimer's disease.NPJ dementia · 2026Article
- Precision Drug Repurposing (PDR): Patient-level modeling and prediction combining foundational knowledge graph with biobank data.Journal of biomedical informatics · 2025Article
- Alzheimer's disease heterogeneity and co-pathologies: Defining novel targets, biomarkers, modalities, and research methodologies.Alzheimer's & dementia (New York, N. Y.)Review
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15 authors at 3 institutions in 2 countries.
Funding
Abstract
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 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.
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, respectively. They matched clinical subtypes and brain atrophy at specific regions. DISCUSSION: Our findings demonstrate that polygenic profiling based on co-expressed gene sets can explain heterogeneity in AD patients, enabling genetically informed patient stratification and precision medicine in AD. HIGHLIGHTS: Co-expression gene-network analysis in Alzheimer's disease (AD) brains identified gene sets (modules) associated with AD heterogeneity. AD-associated modules were selected when genes in each module were enriched for neuritic plaques and neurofibrillary tangles. Polygenic risk scores from two selected modules were linked to the matching cognitively defined AD subgroups (language and visuospatial subgroups). Polygenic risk scores from the two modules were associated with cognitive performance in language and visuospatial domains and the associations were confirmed in regional-specific brain atrophy data.
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