ArticleeLife2025
A microglia clonal inflammatory disorder in Alzheimer's disease.
Article in eLife, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
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- Human iPSC-derived alveolar macrophages reveal macrophage subtype functions of itaconate in M. tuberculosis defense.JCI insight · 2026Article
- Aging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions.Aging cell · 2026Review
- Neuroimmune Interactions in Neurodegeneration: The Role of Microglia in Alzheimer's and Parkinson's Disease Pathogenesis.Brain sciences · 2026Review
- Activating Ras-MAPK pathway variants drive hippocampal clonal competition in human epilepsy.bioRxiv : the preprint server for biology · 2026Article
- Accurate detection of somatic single-nucleotide variants from bulk RNA-seq data using RNA-MosaicHunter.Nucleic acids research · 2026Article
- Basic Microglial Functions and How They Go Awry in Neurodegenerative Disease.Annual review of pathology · 2026Review
- Characterization of the mammalian prodefinitive angio-hematopoietic lineage.Science immunology · 2025Article
- Somatic mutation and selection at population scale.Nature · 2025Article
- Brain somatic mutations in Alzheimer's disease: linking genetic mosaicism to neurodegeneration.Molecular neurodegeneration · 2025Review
- Article
- Article
- BRAFV600E induces key features of LCH in iPSCs with cell type-specific phenotypes and drug responses.Blood · 2025Article
- Somatic Mosaicism in Brain Disorders.Annual review of pathology · 2025Review
- Role of macrophages in neuroimmune regulation.Frontiers in immunology · 2025Review
- Mechanisms and environmental factors shaping the ecosystem of brain macrophages.Frontiers in immunology · 2025Review
- Mutations in Mig6 reduce inhibition of the epidermal growth factor receptor.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Mechanism of neurodegeneration mediated by clonal inflammatory microglia.bioRxiv : the preprint server for biology · 2024Article
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26 authors.
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Abstract
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however, few studies have investigated its role in neurodegenerative processes such as Alzheimer's disease (AD). Here, we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both in vitro and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in humans, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients.
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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 Socratic graph.