ArticleHuman molecular genetics2014
Functional screening in Drosophila identifies Alzheimer's disease susceptibility genes and implicates Tau-mediated mechanisms.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 3 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 3 syntheses or guidelines pooled it, 178 citations in OpenAlex.
- Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.Nature genetics · 2019Pooled it
- FERMT2 rs17125944 polymorphism with Alzheimer's disease risk: a replication and meta-analysis.Oncotarget · 2016Pooled it
- Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease.Nature genetics · 2013Pooled it
- Risk prediction for sporadic Alzheimer's disease using genetic risk score in the Han Chinese population.Oncotarget · 2015Trial
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- 5-ALA/SFC Mitigates Tau Toxicity via Lowering Oxidative Stress in aLife (Basel, Switzerland) · 2026Article
- Immuno-Regulation of Brain Region-Specific Organoids Containing Isogenic Microglia-Like Cells.Advanced healthcare materials · 2026Article
- Prefoldin 5 is a microtubule-associated protein that suppresses Tau aggregation and neurotoxicity.eLife · 2026Article
- Spatial and single-cell transcriptomics reveal the reorganization of cerebellar microglia with aging.Cell reports · 2025Article
- Exploring the versatility ofFly · 2025Review
- CD2AP at the junction of nephropathy and Alzheimer's disease.Molecular neurodegeneration · 2025Review
- An integrative systems-biology approach defines mechanisms of Alzheimer's disease neurodegeneration.Nature communications · 2025Article
- Ptprd deficiency promotes tau hyperphosphorylation and impairs cognitive function in aged mice.Biological research · 2025Article
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- A New Molecular Mechanism for the Late-Onset Alzheimer's Disease Risk Gene CD2AP.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- CD2AP deficiency aggravates Alzheimer's disease phenotypes and pathology through p38 MAPK activation.Translational neurodegeneration · 2024Article
- Microglial CD2AP deficiency exerts protection in an Alzheimer's disease model of amyloidosis.Molecular neurodegeneration · 2024Article
- The Alzheimer's Disease Risk Gene CD2AP Functions in Dendritic Spines by Remodeling F-Actin.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Brazilian kefir fraction mitigates the Alzheimer-like phenotype in Drosophila melanogaster with β-amyloid overexpression model.Scientific reports · 2024Article
- Alzheimer's disease risk gene CD2AP is a dose-sensitive determinant of synaptic structure and plasticity.Human molecular genetics · 2024Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Using a Drosophila model of Alzheimer's disease (AD), we systematically evaluated 67 candidate genes based on AD-associated genomic loci (P < 10(-4)) from published human genome-wide association studies (GWAS). Genetic manipulation of 87 homologous fly genes was tested for modulation of neurotoxicity caused by human Tau, which forms neurofibrillary tangle pathology in AD. RNA interference (RNAi) targeting 9 genes enhanced Tau neurotoxicity, and in most cases reciprocal activation of gene expression suppressed Tau toxicity. Our screen implicates cindr, the fly ortholog of the human CD2AP AD susceptibility gene, as a modulator of Tau-mediated disease mechanisms. Importantly, we also identify the fly orthologs of FERMT2 and CELF1 as Tau modifiers, and these loci have been independently validated as AD susceptibility loci in the latest GWAS meta-analysis. Both CD2AP and FERMT2 have been previously implicated with roles in cell adhesion, and our screen additionally identifies a fly homolog of the human integrin adhesion receptors, ITGAM and ITGA9, as a modifier of Tau neurotoxicity. Our results highlight cell adhesion pathways as important in Tau toxicity and AD susceptibility and demonstrate the power of model organism genetic screens for the functional follow-up of human GWAS.
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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.