ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2021
Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Meta-evolutionary exome analysis identifies novel type 2 diabetes mellitus genes in the UK Biobank and all of us.PLoS genetics · 2025Pooled it
- Proteomic profiling of brain organoids and extracellular vesicles identifies early Alzheimer's disease biomarkers and drug response heterogeneity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Apolipoprotein E drives microglia activation in the development of autoimmune uveitis through up-regulation of peptidyl prolyl isomerase F.Science advances · 2026Article
- Revealing the nervous system requirements of Alzheimer disease risk genes in Drosophila.American journal of human genetics · 2025Article
- Revealing the nervous system requirements of Alzheimer's disease risk genes inbioRxiv : the preprint server for biology · 2025Article
- Endocrine and cellular physiology and pathology of the insulin-like growth factor acid-labile subunit.Nature reviews. Endocrinology · 2024Review
- Evolutionary Action-Machine Learning Model Identifies Candidate Genes Associated With Early-Onset Coronary Artery Disease.Journal of the American Heart Association · 2023Article
- Functional variants identify sex-specific genes and pathways in Alzheimer's Disease.Nature communications · 2023Article
- Integration of transcriptome-wide association study with neuronal dysfunction assays provides functional genomics evidence for Parkinson's disease genes.Human molecular genetics · 2023Article
- Genome interpretation using in silico predictors of variant impact.Human genetics · 2022Review
- Identification of risk genes for Alzheimer's disease by gene embedding.Cell genomics · 2022Article
- EPIMUTESTR: a nearest neighbor machine learning approach to predict cancer driver genes from the evolutionary action of coding variants.Nucleic acids research · 2022Article
- Evolutionary action of mutations reveals antimicrobial resistance genes in Escherichia coli.Nature communications · 2022Article
- An integrated brain-specific network identifies genes associated with neuropathologic and clinical traits of Alzheimer's disease.Briefings in bioinformatics · 2022Article
- Harnessing the paradoxical phenotypes of APOE ɛ2 and APOE ɛ4 to identify genetic modifiers in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2021Article
- Random forest-integrated analysis in AD and LATE brain transcriptome-wide data to identify disease-specific gene expression.PloS one · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The strongest genetic risk factor for idiopathic late-onset Alzheimer's disease (LOAD) is apolipoprotein E (APOE) ɛ4, while the APOE ɛ2 allele is protective. However, there are paradoxical APOE ɛ4 carriers who remain disease-free and APOE ɛ2 carriers with LOAD. We compared exomes of healthy APOE ɛ4 carriers and APOE ɛ2 Alzheimer's disease (AD) patients, prioritizing coding variants based on their predicted functional impact, and identified 216 genes with differential mutational load between these two populations. These candidate genes were significantly dysregulated in LOAD brains, and many modulated tau- or β42-induced neurodegeneration in Drosophila. Variants in these genes were associated with AD risk, even in APOE ɛ3 homozygotes, showing robust predictive power for risk stratification. Network analyses revealed involvement of candidate genes in brain cell type-specific pathways including synaptic biology, dendritic spine pruning and inflammation. These potential modifiers of LOAD may constitute novel biomarkers, provide potential therapeutic intervention avenues, and support applying this approach as larger whole exome sequencing cohorts become available.
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.