ArticleCell2026
Somatic cancer variants enriched in Alzheimer's disease microglia-like cells drive inflammatory and proliferative states.
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In one paragraph
Article in Cell, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
What it found
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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.
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Who cites it
6 citing papers in PubMed.
- Multi-Component Xinjiang Basil Essential Oil Mitigates Alzheimer's Disease-like Pathology Through Amyloid and Neuroinflammatory Modulation.Nutrients · 2026Article
- Somatic mosaicism in the brain: linking development, ageing and neurodegeneration.Nature reviews. Neurology · 2026Review
- Ontogeny and Identity of Tissue Macrophages in Human Aging: Lessons From Brain for the Heart.JACC. Basic to translational science · 2026Article
- Review
- Microglial clonal dynamics and the impact of clonal hematopoiesis in autologously transplanted rhesus macaques.Cell reports · 2026Article
- Clonal hematopoiesis in Alzheimer's brain: Protective, pathogenic, and context-dependent?Trends in molecular medicine · 2026Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors.
August Yue HuangDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: yue.huang@childrens.harvard.edu.
Zinan ZhouDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Maya TalukdarDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard-MIT MD/PhD Program, Boston, MA, USA.
Liz EnyenihiDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard-MIT MD/PhD Program, Boston, MA, USA.
Michael B MillerDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Division of Neuropathology, Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Brian ChhoukDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA.
Ila RosenDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA.
Mengyue ZhengDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Minye ZhouDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA.
Averill YangDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA.
Edward StrongeDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Harvard-MIT MD/PhD Program, Boston, MA, USA.
Madel DurensNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Minh NguyenDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Stem Cell Biology and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Jaejoon ChoiDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Boxun ZhaoDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Sattar KhoshkhooDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.
Junho KimDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Biological Sciences, Sungkyunkwan University, Suwon, South Korea.
Rebecca AndersenDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Zheming AnDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yuchen ChengDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Javier GanzDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Levan MekerishviliNew York Genome Center, New York, NY, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA; Physiology, Biophysics and Systems Biology Graduate Program, Weill Cornell Medicine, New York, NY, USA.
Kyle J TravagliniAllen Institute for Brain Science, Seattle, WA, USA.
Mariano I GabittoAllen Institute for Brain Science, Seattle, WA, USA.
Rebecca D HodgeAllen Institute for Brain Science, Seattle, WA, USA.
Eitan S KaplanAllen Institute for Brain Science, Seattle, WA, USA.
Julia A BelkDepartment of Computer Science, Stanford University, Stanford, CA, USA.
Dan LandauNew York Genome Center, New York, NY, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.
Ed S LeinAllen Institute for Brain Science, Seattle, WA, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology, Department of Neurology and The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical College, Chicago, IL, USA.
Samuele G MarroNash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Stem Cell Biology and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: samuele.marro@mssm.edu.
Eirini P PapapetrouDepartment of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Tisch Cancer Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Stem Cell Biology and Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: eirini.papapetrou@mssm.edu.
Eunjung Alice LeeDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: ealice.lee@childrens.harvard.edu.
Christopher A WalshDivision of Genetics and Genomics and Manton Center for Orphan Diseases, Boston Children's Hospital, Boston, MA, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Howard Hughes Medical Institute, Boston, MA, USA; Department of Neurology, Harvard Medical School, Boston, MA, USA. Electronic address: christopher.walsh@childrens.harvard.edu.
Funding
Topographic, cell type and molecular pathway characterization ofAlzheimer's disease using single cell transcriptomics and epigenomicsU19AG060909 · NIA · ALLEN INSTITUTE · PI Jennie Leigh Close · 2020 to 2026
$83.6MMedical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0MSUPPLEMENT TO RUSH ALZHEIMERS DISEASE CENTER COREP30AG010161 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1991 to 2020
$49.1MEPIDEMIOLOGY OF NEURAL RESERVE AND NEUROBIOLOGY IN AGINGR01AG017917 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 2001 to 2023
$43.3MRush Alzheimer's Disease Research CenterP30AG072975 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI Lisa L Barnes, Julie A. Schneider · 2021 to 2026
$24.7MRISK FACTORS, PATHOLOGY, AND CLINICAL EXPRESSIONS OF ADR01AG015819 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI BENNETT, DAVID ALAN · 1998 to 2024
$21.4MWhole Genome Sequencing and Admixture Analyses of Neuropathologic Traits in White, Black, and Latino Americans and BraziliansR01AG075927 · NIA · RUSH UNIVERSITY MEDICAL CENTER · PI DAVID ALAN BENNETT · 2023 to 2026
$14.9MMedical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7MMulti-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7MPathway discovery, validation and compound identification for Alzheimer's disease - SupplementU01AG046152 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2013 to 2017
$13.6MVASCULAR, PULMONARY AND RENAL INJURYT32HL007627 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI GIMBRONE, MICHAEL A, MITCHELL, RICHARD N · 1985 to 2019
$12.7MCell Identity Determination In Human Brain: Somatic Mutation and Cell LineageR01NS032457 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI Alice Eunjung Lee, Christopher A. Walsh · 1995 to 2026
$12.7MNCI NIH HHS R01 CA260711NCI NIH HHS R01 CA271331NCI NIH HHS R01 CA271418NHLBI NIH HHS T32 HL007627NIA NIH HHS DP2 AG072437NIA NIH HHS DP2 AG086138NIA NIH HHS K08 AG065502NIA NIH HHS P30 AG010161NIA NIH HHS P30 AG072975NIA NIH HHS R01 AG015819NIA NIH HHS R01 AG017917NIA NIH HHS R01 AG070921NIA NIH HHS R01 AG075927NIA NIH HHS R01 AG078929NIA NIH HHS R01 AG082346NIA NIH HHS R01 AG088082NIA NIH HHS R56 AG079857NIA NIH HHS U01 AG046152NIA NIH HHS U01 AG061356NIA NIH HHS U19 AG060909NIGMS NIH HHS T32 GM007748NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM141745NIGMS NIH HHS T32 GM144273NINDS NIH HHS K08 NS128272NINDS NIH HHS L30 NS118655NINDS NIH HHS R01 NS032457NINDS NIH HHS R25 NS065743NINDS NIH HHS UG3 NS132138NINDS NIH HHS UG3 NS132144NINDS NIH HHS UH3 NS132138
Abstract
Alzheimer's disease (AD) is a neurodegenerative condition characterized by microglia-mediated neuroinflammation. Deep (>1,000×) panel sequencing of 311 brain samples revealed enrichment of somatic single-nucleotide variants (sSNVs) in cancer driver genes in AD brains, especially in genes associated with clonal hematopoiesis (CH). These sSNVs were associated with clonal expansion and carried by both microglia-like brain macrophages (MLBMs) in multiple brain regions as well as paired blood, suggesting a likely hematopoietic origin. Single-nucleus RNA sequencing data from 62 additional AD and control brains revealed increased somatic copy number variants (sCNVs) associated with CH in AD MLBMs, whereas single-cell multi-omic analyses demonstrated that sSNV- and sCNV-carrying MLBMs exhibited inflammatory and proliferative transcriptional signatures characteristic of disease-associated microglia. These signatures were recapitulated in induced pluripotent stem cell-derived microglia-like cells with TET2, ASXL1, and DNMT3A variants. These findings suggest that clonal somatic driver variants in MLBMs are enriched in AD, potentially promoting neuroinflammation and neurodegeneration.
Indexed as
Alzheimer DiseaseInflammationMicrogliaAnimalsBrainCell ProliferationClonal HematopoiesisDNA Copy Number VariationsHumansMacrophagesAlzheimer’s diseasebrain macrophageclonal expansionmicrogliasomatic variant
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