ArticleGenome medicine2017
Linkage, whole genome sequence, and biological data implicate variants in RAB10 in Alzheimer's disease resilience.
Article in Genome medicine, 2017. 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 58 papers, 2 of them syntheses 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
58 citing papers in PubMed, 2 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Genetic Variants Associated With Resilience in Human and Animal Studies.Frontiers in psychiatry · 2022Pooled it
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- Alzheimer's disease: genetic background in the era of next-generation sequencing technologies.Brain communications · 2026Review
- LRRK2 kinase-mediated accumulation of lysosome-associated phospho-Rabs in tauopathies and synucleinopathies.Acta neuropathologica · 2025Article
- Rab10 inactivation promotes AMPAR trafficking and spine enlargement during long-term potentiation.eLife · 2025Article
- Rab10 inactivation promotes AMPAR trafficking and spine enlargement during long-term potentiation.bioRxiv : the preprint server for biology · 2025Article
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
- Extracellular vesicle signatures from eye lavage as novel non-invasive biomarkers for hypoxic ischaemic insult-findings from a neonatal mouse model.Frontiers in medical technology · 2025Article
- Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- SAR1A Induces Cell Growth and Epithelial-Mesenchymal Transition Through the PI3K/AKT/mTOR Pathway in Head and Neck Squamous Cell Carcinoma: An In Vitro and In Vivo Study.Biomedicines · 2024Article
- Impairment of the Glial Phagolysosomal System Drives Prion-Like Propagation in aThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- The concept of resilience to Alzheimer's Disease: current definitions and cellular and molecular mechanisms.Molecular neurodegeneration · 2024Review
- The LRRK2 kinase substrates RAB8a and RAB10 contribute complementary but distinct disease-relevant phenotypes in human neurons.Stem cell reports · 2024Article
- Impairment of the glial phagolysosomal system drives prion-like propagation in abioRxiv : the preprint server for biology · 2024Article
- MicroRNAs dysregulated in multiple sclerosis affect the differentiation of CG-4 cells, an oligodendrocyte progenitor cell line.Frontiers in cellular neuroscience · 2024Article
- Role of Rab10 in cocaine-induced behavioral effects is associated with GABAB receptor membrane expression in the nucleus accumbens.Frontiers in pharmacology · 2024Article
- Quantitative proteomic analysis using a mouse model of Lewy body dementia induced by α-synuclein preformed fibrils injection.Frontiers in dementia · 2024Article
- Cellular and subcellular localization of Rab10 and phospho-T73 Rab10 in the mouse and human brain.Acta neuropathologica communications · 2023Article
- Genetic analysis of cognitive preservation in the midwestern Amish reveals a novel locus on chromosome 2.medRxiv : the preprint server for health sciences · 2023Article
- Article
Corrections and comments
- Erratum issued
Authors and funding
32 authors at 8 institutions in 2 countries.
Funding
Abstract
backgroundWhile age and the APOE ε4 allele are major risk factors for Alzheimer's disease (AD), a small percentage of individuals with these risk factors exhibit AD resilience by living well beyond 75 years of age without any clinical symptoms of cognitive decline.
methodsWe used over 200 "AD resilient" individuals and an innovative, pedigree-based approach to identify genetic variants that segregate with AD resilience. First, we performed linkage analyses in pedigrees with resilient individuals and a statistical excess of AD deaths. Second, we used whole genome sequences to identify candidate SNPs in significant linkage regions. Third, we replicated SNPs from the linkage peaks that reduced risk for AD in an independent dataset and in a gene-based test. Finally, we experimentally characterized replicated SNPs.
resultsRs142787485 in RAB10 confers significant protection against AD (p value = 0.0184, odds ratio = 0.5853). Moreover, we replicated this association in an independent series of unrelated individuals (p value = 0.028, odds ratio = 0.69) and used a gene-based test to confirm a role for RAB10 variants in modifying AD risk (p value = 0.002). Experimentally, we demonstrated that knockdown of RAB10 resulted in a significant decrease in Aβ42 (p value = 0.0003) and in the Aβ42/Aβ40 ratio (p value = 0.0001) in neuroblastoma cells. We also found that RAB10 expression is significantly elevated in human AD brains (p value = 0.04).
conclusionsOur results suggest that RAB10 could be a promising therapeutic target for AD prevention. In addition, our gene discovery approach can be expanded and adapted to other phenotypes, thus serving as a model for future efforts to identify rare variants for AD and other complex human diseases.
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.