ArticleNature communications2019
Brain somatic mutations observed in Alzheimer's disease associated with aging and dysregulation of tau phosphorylation.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 158 citations in OpenAlex.
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
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- RNA isoform diversity, splicing variants and switching in single cells of the Alzheimer's disease brain.Communications biology · 2026Article
- Spatial phosphoproteomics reveals regional phosphorylation features in liver cirrhosis progression.Journal of translational medicine · 2026Article
- Accurate detection of somatic single-nucleotide variants from bulk RNA-seq data using RNA-MosaicHunter.Nucleic acids research · 2026Article
- Alzheimer's disease: genetic background in the era of next-generation sequencing technologies.Brain communications · 2026Review
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- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- Increased nucleotide metabolism alleviates Alzheimer's disease pathology.Cell death & disease · 2025Article
- Brain somatic mutations in Alzheimer's disease: linking genetic mosaicism to neurodegeneration.Molecular neurodegeneration · 2025Review
- RNA isoform diversity, splicing variants, and switching in single cells of the Alzheimer's disease brain.Research square · 2025Article
- The Somatic Mosaicism across Human Tissues Network.Nature · 2025Review
- Sequence Diversity and Encoded Enzymatic Differences of Monocistronic L1 ORF2 mRNA Variants in the Aged Normal and Alzheimer's Disease Brain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Characterization of prion strains and peripheral prion infectivity patterns in E200K genetic CJD patients.Acta neuropathologica · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Article
- Distant origin of glioblastoma recurrence: neural stem cells in the subventricular zone serve as a source of tumor reconstruction after primary resection.Molecular cancer · 2025Article
- The genetic landscape of early-onset Alzheimer's disease in China.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- DeepDrug as an expert guided and AI driven drug repurposing methodology for selecting the lead combination of drugs for Alzheimer's disease.Scientific reports · 2025Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
The role of brain somatic mutations in Alzheimer's disease (AD) is not well understood. Here, we perform deep whole-exome sequencing (average read depth 584×) in 111 postmortem hippocampal formation and matched blood samples from 52 patients with AD and 11 individuals not affected by AD. The number of somatic single nucleotide variations (SNVs) in AD brain specimens increases significantly with aging, and the rate of mutation accumulation in the brain is 4.8-fold slower than that in AD blood. The putatively pathogenic brain somatic mutations identified in 26.9% (14 of 52) of AD individuals are enriched in PI3K-AKT, MAPK, and AMPK pathway genes known to contribute to hyperphosphorylation of tau. We show that a pathogenic brain somatic mutation in PIN1 leads to a loss-of-function mutation. In vitro mimicking of haploinsufficiency of PIN1 aberrantly increases tau phosphorylation and aggregation. This study provides new insights into the genetic architecture underlying the pathogenesis of AD.
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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 OpenQuestion graph.