10.1016\/j.cell.2026.03.040<\/a>), the study uncovered a potential new biological mechanism linking aging, immune dysfunction, and Alzheimer’s disease. The findings suggest that age-related mutations in microglia\u2014the brain’s primary immune cells\u2014may alter how these cells function, promoting inflammatory activity associated with disease progression.<\/p>\nAlzheimer’s disease affects millions of people worldwide and is characterized by progressive memory loss, cognitive decline, and neurodegeneration. Although inflammation is known to play a central role in the disease, the factors that trigger harmful immune responses in the brain are not fully understood.<\/p>\n
The research team found that somatic mutations\u2014DNA changes acquired during life rather than inherited at birth\u2014were enriched in microglia-like immune cells in Alzheimer’s disease brains. Many of these mutations occurred in genes previously linked to clonal hematopoiesis, an age-related condition in which blood stem cells acquire mutations and expand disproportionately over time.<\/p>\n
Using ultra-deep genetic sequencing, single-cell analyses, and stem cell-based laboratory models, the researchers demonstrated that these mutations may push brain immune cells into inflammatory and proliferative states associated with Alzheimer\u2019s disease progression.<\/p>\n
A New Perspective on Alzheimer’s Disease <\/p>\n
\u201cOur data suggest that some immune cells in Alzheimer\u2019s disease undergo genetic changes over time that alter their behavior and potentially contribute to chronic inflammation in the brain,\u201d said Samuele Marro, PhD, Associate Professor in the Nash Family Department of Neuroscience and The Friedman Brain Institute at Mount Sinai, and co-corresponding author of the study. “These findings provide a new framework for understanding how aging, immune dysfunction, and neurodegeneration may intersect in Alzheimer’s disease.”<\/p>\n
Microglia play an essential role in maintaining healthy brain function by clearing cellular debris, regulating synaptic activity, responding to injury, and helping regulate immune activity in the central nervous system. Previous research has shown that these cells can become abnormally activated in Alzheimer\u2019s disease, contributing to inflammation and neuronal damage. However, the biological mechanisms driving this harmful transformation have remained unclear.<\/p>\n
To investigate, the research team analyzed 311 postmortem brain samples from patients with Alzheimer\u2019s disease and age-matched controls using ultra-deep sequencing of 149 genes commonly associated with cancer and clonal hematopoiesis. They found significantly more somatic mutations in Alzheimer\u2019s disease brains, particularly in the genes TET2, DNMT3A, and ASXL1.<\/p>\n
Many of the mutations were highly enriched in microglia-like brain cells and largely absent in neurons. Researchers also detected many of the same mutations in matched blood samples, suggesting that mutated blood-derived immune cells may infiltrate the brain and adopt microglia-like functions.<\/p>\n
\u201cOur study provides functional evidence that mutations commonly associated with aging blood cells and cancer biology can directly alter the behavior of brain immune cells,\u201d said co-corresponding author of the study, Eirini Papapetrou, MD, PhD, Professor of Oncological Sciences at the Icahn School of Medicine at Mount Sinai and Director of the Center for Advancement of Blood Cancer Therapies at Mount Sinai. \u201cThese mutated cells showed inflammatory signatures strongly associated with neurodegeneration.\u201d<\/p>\n
The researchers further validated their findings using induced pluripotent stem cell-derived microglia-like cells engineered with CRISPR to carry mutations found in Alzheimer\u2019s disease samples. Cells carrying the mutations adopted inflammatory gene expression patterns and disease-associated microglial states previously linked to neurodegeneration.<\/p>\n
Implications for Future Research and Treatment<\/p>\n
The findings suggest that age-related accumulation of mutations in immune cells may represent a previously underrecognized contributor to Alzheimer\u2019s disease biology and could eventually inform the development of new therapeutic strategies.<\/p>\n
\u201cThis work highlights a potentially important connection between aging blood biology and neurodegenerative disease,\u201d said Dr. Marro. \u201cIf confirmed in future studies, these findings could open new avenues for therapies that target harmful inflammatory immune cell populations in the brain.\u201d<\/p>\n
The authors caution that the findings do not prove that these mutations cause Alzheimer\u2019s disease. Rather, they identify an association and a potential mechanism that warrants further investigation. Future studies will focus on validating the findings in animal models and exploring whether targeting mutated immune cell populations could help slow neurodegeneration.<\/p>\n
The study was supported by grants from the National Institutes of Health, the Alzheimer\u2019s Association, the BrightFocus Foundation, the Edward P. Evans Foundation, and other institutional and philanthropic sources.<\/p>\n
In addition to investigators at Mount Sinai and Boston Children\u2019s Hospital, investigators from the Broad Institute of MIT and Harvard, Columbia University, Rush University Medical Center, the Allen Institute for Brain Science, Weill Cornell Medicine, and the New York Genome Center contributed to the research.<\/p>\n
Full study and list of authors: https:\/\/www.cell.com\/cell\/fulltext\/S0092-8674(26)00341-7<\/a><\/p>\n###<\/p>\n
About the Icahn School of Medicine at Mount Sinai<\/p>\n
The Icahn School of Medicine at Mount Sinai is internationally renowned for its outstanding research, educational, and clinical care programs. It is the sole academic partner for the seven member hospitals* of the Mount Sinai Health System, one of the largest academic health systems in the United States, providing care to New York City\u2019s large and diverse patient population.\u00a0<\/p>\n
The Icahn School of Medicine at Mount Sinai offers highly competitive MD, PhD, MD-PhD, and master\u2019s degree programs, with enrollment of more than 1,200 students. It has the largest graduate medical education program in the country, with more than 2,700 clinical residents and fellows training throughout the Health System. The Graduate School of Biomedical Sciences offers 13 degree-granting programs, conducts innovative basic and translational research, and trains more than 4705 postdoctoral research fellows.<\/p>\n
Ranked 11th nationwide in National Institutes of Health (NIH) funding, the Icahn School of Medicine at Mount Sinai is among the 90th percentile of U.S. private medical schools in Sponsored Programs Direct Expenditures per Principal Investigator, according to the Association of American Medical Colleges.\u00a0 More than 6,900 scientists, educators, and clinicians work within and across dozens of academic departments and multidisciplinary institutes with an emphasis on translational research and therapeutics. Through Mount Sinai Innovation Partners (MSIP), the Health System facilitates the real-world application and commercialization of medical breakthroughs made at Mount Sinai.<\/p>\n
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* Mount Sinai Health System member hospitals: The Mount Sinai Hospital; Mount Sinai Brooklyn; Mount Sinai Morningside; Mount Sinai Queens; Mount Sinai South Nassau; Mount Sinai West; and New York Eye and Ear Infirmary of Mount Sinai. \u00a0<\/p>\n","protected":false},"excerpt":{"rendered":"Cancer-Associated Mutations in Brain Immune Cells May Contribute to Alzheimer’s Disease Mount Sinai-led study identifies age-related genetic changes…\n","protected":false},"author":2,"featured_media":302845,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[8264,134,111,2055,139,69],"class_list":["post-472280","post","type-post","status-publish","format-standard","has-post-thumbnail","category-health","tag-alzheimer","tag-health","tag-new-zealand","tag-newswise","tag-newzealand","tag-nz"],"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/472280","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/comments?post=472280"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/posts\/472280\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media\/302845"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/media?parent=472280"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/categories?post=472280"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/nz\/wp-json\/wp\/v2\/tags?post=472280"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}