ArticleMolecular neurodegeneration2023
Genome-wide association study of brain biochemical phenotypes reveals distinct genetic architecture of Alzheimer's disease related proteins.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Pooled it
- Elucidating the neuropathological and molecular heterogeneity of amyloid beta and tau in Alzheimer's disease through machine learning and transcriptomic integration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- 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
- Concordance of cortical morphological anomalies with genetic predisposition to multisite chronic pain in females.The Korean journal of pain · 2026Article
- Integrative epigenomic landscape of Alzheimer's Disease brains reveals oligodendrocyte molecular perturbations associated with tau.Nature communications · 2026Article
- Brain multiomic profiling identifies tau-related transcriptomic dysregulation in Alzheimer's disease.Brain communications · 2026Article
- Article
- Linking DNA methylation in brain regions to Alzheimer's disease risk: a Mendelian randomization study.Human molecular genetics · 2025Article
- Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease.Journal of neurochemistry · 2024Review
- Genomic study of taste perception genes in African Americans reveals SNPs linked to Alzheimer's disease.Scientific reports · 2024Article
- Proteomic Mendelian randomization to identify protein biomarkers of telomere length.Scientific reports · 2024Article
- p53 target ANKRA2 cooperates with RFX7 to regulate tumor suppressor genes.Cell death discovery · 2024Article
- Genomic Study of Taste Perception Genes in African Americans Reveals SNPs Linked to Alzheimer's Disease.bioRxiv : the preprint server for biology · 2024Article
- Unraveling the genetic architecture of blood unfolded p-53 among non-demented elderlies: novel candidate genes for early Alzheimer's disease.BMC genomics · 2024Article
- Bridging the Gap: Multi-Omics Profiling of Brain Tissue in Alzheimer's Disease and Older Controls in Multi-Ethnic Populations.bioRxiv : the preprint server for biology · 2024Article
- Top 100 most-cited articles on tau protein: a bibliometric analysis and evidence mapping.Frontiers in neuroscience · 2024Article
- The Association of Selected GWAS Reported AD Risk Loci with CSF Biomarker Levels and Cognitive Decline in Slovenian Patients.International journal of molecular sciences · 2023Article
- Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.Acta neuropathologica communications · 2023Article
- X chromosome-wide association study of quantitative biomarkers from the Alzheimer's Disease Neuroimaging Initiative study.Frontiers in aging neuroscience · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAlzheimer's disease (AD) is neuropathologically characterized by amyloid-beta (Aβ) plaques and neurofibrillary tangles. The main protein components of these hallmarks include Aβ40, Aβ42, tau, phosphor-tau, and APOE. We hypothesize that genetic variants influence the levels and solubility of these AD-related proteins in the brain; identifying these may provide key insights into disease pathogenesis.
methodsGenome-wide genotypes were collected from 441 AD cases, imputed to the haplotype reference consortium (HRC) panel, and filtered for quality and frequency. Temporal cortex levels of five AD-related proteins from three fractions, buffer-soluble (TBS), detergent-soluble (Triton-X = TX), and insoluble (Formic acid = FA), were available for these same individuals. Variants were tested for association with each quantitative biochemical measure using linear regression, and GSA-SNP2 was used to identify enriched Gene Ontology (GO) terms. Implicated variants and genes were further assessed for association with other relevant variables.
resultsWe identified genome-wide significant associations at seven novel loci and the APOE locus. Genes and variants at these loci also associate with multiple AD-related measures, regulate gene expression, have cell-type specific enrichment, and roles in brain health and other neuropsychiatric diseases. Pathway analysis identified significant enrichment of shared and distinct biological pathways.
conclusionsAlthough all biochemical measures tested reflect proteins core to AD pathology, our results strongly suggest that each have unique genetic architecture and biological pathways that influence their specific biochemical states in the brain. Our novel approach of deep brain biochemical endophenotype GWAS has implications for pathophysiology of proteostasis in AD that can guide therapeutic discovery efforts focused on these proteins.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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 OpenQuestion graph.