ArticleThe EMBO journal2021
PIP2 depletion and altered endocytosis caused by expression of Alzheimer's disease-protective variant PLCγ2 R522.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 37 citations in OpenAlex.
- Single-cell-level perturbation-induced and condition-related signal estimation with batch effect removal using NDreamer.Briefings in bioinformatics · 2026Article
- Article
- PLCγ2 deficiency compromises systemic immune tolerance and erodes myelin homeostasis while enhancing oxidative metabolism in the mouse brain.bioRxiv : the preprint server for biology · 2026Article
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- Are we fully exploiting genetic discoveries to understand and treat Alzheimer's disease?Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- PLCG2 across human disease: genetic variants, signaling mechanisms, and clinical implications.Journal of translational medicine · 2026Review
- Alzheimer's disease-associated PLCG2 variants alter microglial state and function in human induced pluripotent stem cell-derived microglia-like cells.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- A high-throughput assay platform to discover small molecule activators of the phospholipase PLC-γ2 to treat Alzheimer's disease.The Journal of biological chemistry · 2025Article
- The protective PLCγ2-P522R variant mitigates Alzheimer's disease-associated pathologies by enhancing beneficial microglial functions.Journal of neuroinflammation · 2025Article
- Lipidome disruption in Alzheimer's disease brain: detection, pathological mechanisms, and therapeutic implications.Molecular neurodegeneration · 2025Review
- The crystal and cryo-EM structures of PLCγ2 reveal dynamic interdomain recognitions in autoinhibition.Science advances · 2024Article
- Elevated expression of the retrotransposon LINE-1 drives Alzheimer's disease-associated microglial dysfunction.Acta neuropathologica · 2024Article
- Alzheimer's disease-associated protective variant Plcg2-P522R modulates peripheral macrophage function in a sex-dimorphic manner.Journal of neuroinflammation · 2024Article
- The role of macrophage plasticity in neurodegenerative diseases.Biomarker research · 2024Review
- Endocytosis and Alzheimer's disease.GeroScience · 2024Review
- Multi-omics analyses reveal novel effects of PLCγ2 deficiency in the mouse brain.bioRxiv : the preprint server for biology · 2023Article
- Mutant huntingtin confers cell-autonomous phenotypes on Huntington's disease iPSC-derived microglia.Scientific reports · 2023Article
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- Article
- Carriers of the p.P522R variant in PLCγ2 have a slightly more responsive immune system.Molecular neurodegeneration · 2023Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
Variants identified in genome-wide association studies have implicated immune pathways in the development of Alzheimer's disease (AD). Here, we investigated the mechanistic basis for protection from AD associated with PLCγ2 R522, a rare coding variant of the PLCG2 gene. We studied the variant's role in macrophages and microglia of newly generated PLCG2-R522-expressing human induced pluripotent cell lines (hiPSC) and knockin mice, which exhibit normal endogenous PLCG2 expression. In all models, cells expressing the R522 mutation show a consistent non-redundant hyperfunctionality in the context of normal expression of other PLC isoforms. This manifests as enhanced release of cellular calcium ion stores in response to physiologically relevant stimuli like Fc-receptor ligation or exposure to Aβ oligomers. Expression of the PLCγ2-R522 variant resulted in increased stimulus-dependent PIP
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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.