Evidence map›Paper›PMID 40609533›Full record

ArticleCell stem cell2025

TET2-mutant myeloid cells mitigate Alzheimer's disease progression via CNS infiltration and enhanced phagocytosis in mice.

Katie A Matatall, Trisha K Wathan, Minh Nguyen, Hu Chen, Alexandra McDonald, Guantong Qi, Julia A Belk, Marcus A Florez, Duy T Le, Temitope Olarinde and 19 more

Erratum issuedAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell stem cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

29 authors.

Katie A MatatallDivision of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Trisha K WathanDepartment of Hematopoietic Biology & Malignancy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Minh NguyenDepartments of Oncological Sciences and Medicine, Tisch Cancer 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; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Hu ChenDepartment of Pediatrics, Jan and Dan Duncan Neurological Research Institute, Baylor College of Medicine, Houston, TX 77030, USA; Jan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA.
Alexandra McDonaldDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Guantong QiJan and Dan Duncan Neurologic Research Institute, Texas Children's Hospital, Houston, TX 77030, USA; Graduate School of Biomedical Sciences, Program in Genetics & Genomics, Baylor College of Medicine, Houston, TX 77030, USA.
Julia A BelkDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Marcus A FlorezDepartment of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Duy T LeGraduate School of Biomedical Sciences, Program in Immunology and Microbiology, Baylor College of Medicine, Houston, TX, 77030, USA.
Temitope OlarindeRice University, Houston, TX 77030, USA.
Caitlyn VlasschaertDepartment of Medicine, Queen's University, Kingston, ON, Canada.
Marco M ButtigiegDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada.
Chih-Wei FanDepartments of Oncological Sciences and Medicine, Tisch Cancer 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; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Saul CarcamoDepartments of Oncological Sciences and Medicine, Tisch Cancer 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; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Ruoqiong CaoDivision of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Daniel E KennedyDivision of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Arushana A MaknojiaDivision of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Apoorva ThatavartyDivision of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Josaura V Fernandez SanchezDivision of Hematology Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
Hind BouzidDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Surabi VeeraragavanDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
Susan CrockerDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; Kingston Health Sciences Centre (KHSC), Kingston, Ontario, Canada.
Margaret A GoodellDepartment of Molecular and Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Antony RodriguezDivision of Immunology, Allergy, and Rheumatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.
Siddhartha JaiswalDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Michael J RauhDepartment of Medicine, Queen's University, Kingston, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; Kingston Health Sciences Centre (KHSC), Kingston, Ontario, Canada. Electronic address: rauhm@queensu.ca.
Eirini P PapapetrouDepartments of Oncological Sciences and Medicine, Tisch Cancer 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; Institute for Regenerative Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: eirini.papapetrou@mssm.edu.
Samuele G MarroCenter for Advancement of Blood Cancer Therapies, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: samuele.marro@mssm.edu.
Katherine Y KingDivision of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: katherine.king@bcm.edu.

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DIANE BODURKA · 1985 to 2026
$290.8M
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Suzanne AW Fuqua · 2007 to 2026
$73.9M
Project 3: Contribution of inflammation and DNA damaging factors to clonal expansion and malignant transformation in a community cohort of older adultsP01CA265748 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Daisuke Nakada · 2022 to 2026
$13.6M
Hematology Training ProgramT32DK060445 · NIDDK · BAYLOR COLLEGE OF MEDICINE · PI GOODELL, MARGARET A. · 2002 to 2023
$8.3M
Training In Cell and Gene TherapyT32HL092332 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI MALCOLM K. BRENNER, Bruno Di Stefano · 2008 to 2026
$6.9M
Impact of Infection and Inflammation on Primitive HematopoiesisR35HL155672 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI Katherine Yudeh King · 2021 to 2026
$5.1M
Modeling HIV Microglia-Associated Infection and Inflammation in a Chimeric Mouse BrainR01DA054526 · NIDA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, CHEN, BENJAMIN K · 2021 to 2025
$3.7M
Mechanisms and therapeutic implications of human clonal hematopoiesis (CH) mutationsR01CA271331 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Eirini Papapetrou · 2022 to 2026
$3.3M
Impact of mutational order on molecular mechanisms of oncogenesisR01CA260711 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Eirini Papapetrou · 2022 to 2026
$3.2M
Cell-lineage specific epigenomic determinants of HIV latency in humanized mouse brain and bloodR01MH134319 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Schahram Akbarian, BENJAMIN K CHEN · 2023 to 2026
$2.9M
Mechanisms and targeting of aberrant Gas activation in myeloid neoplasmsR01CA271418 · NCI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Eirini Papapetrou · 2023 to 2026
$2.7M
The Contribution ofInfection to Preleukemic Clonal HematopoiesisR01HL136333 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI KING, KATHERINE YUDEH · 2017 to 2020
$1.9M
NCI NIH HHS P01 CA265748NCI NIH HHS P30 CA016672NCI NIH HHS P30 CA125123NCI NIH HHS R01 CA260711NCI NIH HHS R01 CA271331NCI NIH HHS R01 CA271418NCRR NIH HHS S10 RR024574NHLBI NIH HHS F31 HL154661NHLBI NIH HHS F31 HL156500NHLBI NIH HHS F31 HL168921NHLBI NIH HHS R01 HL136333NHLBI NIH HHS R35 HL155672NHLBI NIH HHS T32 HL092332NIA NIH HHS R56 AG088669NIDA NIH HHS R01 DA054526NIDDK NIH HHS T32 DK060445NIH HHS S10 OD024977NIMH NIH HHS R01 MH134319
6 · The paper itself

Abstract

Clonal hematopoiesis (CH) is associated with many age-related diseases, but its interaction with Alzheimer's disease (AD) remains unclear. Here, we show that TET2-mutant CH is associated with a 47% reduced risk of late-onset AD (LOAD) in the UK Biobank, whereas other drivers of CH do not confer protection. In a mouse model of AD, transplantation of Tet2-mutant bone marrow reduced cognitive decline and β-amyloid plaque formation, effects not observed with Dnmt3a-mutant marrow. Bone-marrow-derived microglia-like cells were detected at an increased rate in Tet2-mutant marrow recipients, and TET2-mutant human induced pluripotent stem cell (iPSC)-derived microglia were more phagocytic and hyperinflammatory than DNMT3A-mutant or wild-type microglia. Strikingly, single-cell RNA sequencing (scRNA-seq) revealed that macrophages and patrolling monocytes were increased in brains of mice transplanted with Tet2-mutant marrow in response to chemokine signaling. These studies reveal a TET2-specific protective effect of CH on AD pathogenesis mediated by peripheral myeloid cell infiltration.

Indexed as

Alzheimer DiseaseCentral Nervous SystemDisease ProgressionDNA-Binding ProteinsMutationMyeloid CellsPhagocytosisProto-Oncogene ProteinsAnimalsBrainClonal HematopoiesisDioxygenasesDisease Models, AnimalDNA Methyltransferase 3AFemaleHumansDioxygenasesDNA-Binding ProteinsDNA Methyltransferase 3AProto-Oncogene ProteinsTET2 protein, humanTet2 protein, mouseAlzheimer’s diseaseclonal hematopoiesisDNMT3Ainflammationmicroglia, peripheral immune cellsmyeloid cell activationphagocytosisTET2

Identifiers

PMID40609533
PMCPMC12233156

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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.