ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2024
Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Functionally informed annotation influences pathway-specific polygenic risk and disease inference in Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- CSF Proteomic Profiles Associated With White Matter Integrity in Cognitively Normal Older Adults With and Without Amyloid Pathology.Neurology · 2026Article
- Advancing global dementia research through equity and inclusion.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cerebrospinal fluid NPTX2 and [Alzheimer's research & therapy · 2025Article
- Polygenic pathways shape white matter vulnerability to Alzheimer's disease-related pathophysiological changes.Alzheimer's research & therapy · 2025Article
- Early detection of Alzheimer's disease using small RNAs. Results from the EPAD cohort.The journal of prevention of Alzheimer's disease · 2025Article
- White-Matter Structural Connectivity and Alzheimer's Disease: A Mendelian Randomization Study.Brain and behavior · 2025Article
- Cell-weighted polygenic risk scores are associated with β-amyloid and tau biomarkers in Alzheimer's disease.Brain communications · 2025Article
- Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Towards cascading genetic risk in Alzheimer's disease.Brain : a journal of neurology · 2024Article
- Pathway-based polygenic risk of Alzheimer's disease highlights immune genes in cognitive decline.Alzheimer's & dementia (New York, N. Y.)Article
Corrections and comments
- Erratum issued
Authors and funding
33 authors.
Funding
Abstract
introductionUnraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine.
methodsWe computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity.
resultsCSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication. DISCUSSION: This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies. HIGHLIGHTS: Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.