Summary: Researchers report a major discovery linking Alzheimer’s disease to the same biological drivers found in certain blood cancers, such as leukemia and lymphoma.
The study shows that as people age, the brain’s immune cells—microglia—accumulate specific cancer-associated mutations. Rather than forming tumors, these mutated cells create an inflammatory, hostile environment that damages and kills neurons. The findings point to the possibility of repurposing existing cancer drugs to treat Alzheimer’s and developing blood-based genetic tests to identify at-risk individuals years before symptoms begin.
Key Findings
- Repurposing cancer drugs: Because Alzheimer’s and some blood cancers share mutations in the same genes, FDA-approved therapies for blood malignancies could potentially be adapted to slow or prevent Alzheimer’s progression.
- New diagnostic potential: The mutations are detectable in blood, opening the door to genetic screens that could identify people at elevated risk long before clinical symptoms appear.
- Somatic mosaicism: The study strengthens evidence that somatic mutations—genetic changes acquired during life—play an important role in neurodegenerative disease.
Source: Boston Children’s Hospital
Overview: New research from Boston Children’s Hospital, published in Cell, examined how somatic (acquired) mutations in microglia are linked to Alzheimer’s disease. The team found enrichment of cancer-driving variants in microglia-like cells from brains affected by Alzheimer’s, suggesting these mutations contribute to inflammation and neuronal loss rather than producing tumors.
The study was led by Christopher A. Walsh, MD, PhD, Chief of the Division of Genetics and Genomics at Boston Children’s Hospital and an Investigator of the Howard Hughes Medical Institute, with key contributions from Alice Eunjung Lee, PhD, and August Yue Huang, PhD. All are professors at Harvard Medical School and affiliated with the Broad Institute. The authors report that their results may inform new diagnostics and targeted therapies for Alzheimer’s disease.
“To some extent, Alzheimer’s disease resembles cancer—driven by some of the same mutations that underlie blood cancers like lymphoma and leukemia,” said Walsh. “This is encouraging because many cancer drugs already exist and some may prove useful against Alzheimer’s.”
The investigators sequenced 149 genes known to drive cancer in tissue from 190 brains donated by people with Alzheimer’s and compared them with tissue from 121 control brains. They found more single-nucleotide changes in the Alzheimer’s samples, concentrated in five recurrent cancer-driver genes, indicating microglia accumulate mutations in specific, functionally relevant genes.
Microglia are the brain’s resident immune cells, responsible for clearing debris, infected cells, and dying neurons. Unlike circulating immune cells, microglia were previously thought to remain behind the blood-brain barrier. The team discovered that many of the cancer-associated mutations identified in brain microglia are the same variants commonly seen in clonal hematopoiesis and blood cancers.
Because of this overlap, the researchers examined blood from the same Alzheimer’s patients and unexpectedly found the same cancer-driving mutations in blood cells. This finding supports a model in which hematopoietic cells bearing somatic driver variants can enter the brain—especially when the blood-brain barrier is weakened by age or injury—and adopt microglia-like roles.
Once in the brain, these mutant cells may have a growth or survival advantage and come to dominate the local microglial population. However, their altered gene programs make them more inflammatory and toxic to surrounding neurons, promoting the neurodegeneration characteristic of Alzheimer’s disease.
“Because brain tissue is hard to access in living patients, developing blood-based genetic screens could offer a practical way to detect these mutations and estimate Alzheimer’s risk,” Lee said.
A follow-up study by Huang and Lee, currently available as a preprint, shows that the presence of cancer driver mutations in blood increases Alzheimer’s risk independently of APOE4, a well-known genetic risk factor.
Funding: The work involved collaborators at Icahn School of Medicine at Mount Sinai and received support from the Howard Hughes Medical Institute, the National Institute on Aging, the NIH Common Fund through the Somatic Mosaicism Across Human Tissues (SMaHT) consortium, and the Suh Kyungbae Foundation (SUHF).
Key Questions Answered:
A: No. Alzheimer’s does not form tumors. Instead, it appears to use a similar mechanism—somatic mutations that let certain immune cells expand and outcompete others. In Alzheimer’s, the dominant cells create a toxic, inflammatory environment rather than a mass.
A: Not yet. The finding is still at the research stage. The investigators are working toward blood-based genetic screens that could eventually be used clinically.
A: Until now, researchers did not realize the genetic targets were shared. Identifying specific mutated genes creates opportunities for precision therapies that selectively target the mutant immune cells while sparing healthy cells.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The referenced journal paper was reviewed in full by the editorial team.
- Additional context and clarifications were provided by staff.
About this genetics, Alzheimer’s disease, and cancer research news
Author: Joelle Zaslow
Source: Boston Children’s Hospital
Contact: Joelle Zaslow – Boston Children’s Hospital
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Somatic cancer variants enriched in Alzheimer’s disease microglia-like cells drive inflammatory and proliferative states” by August Yue Huang et al., published in Cell.
DOI: 10.1016/j.cell.2026.03.040
Abstract
Somatic cancer variants enriched in Alzheimer’s disease microglia-like cells drive inflammatory and proliferative states
Alzheimer’s disease (AD) is a neurodegenerative disorder marked by microglia-driven neuroinflammation. Deep panel sequencing (>1,000×) of 311 brain samples revealed enrichment of somatic single-nucleotide variants (sSNVs) in cancer driver genes in AD brains, particularly in genes linked to clonal hematopoiesis (CH).
These sSNVs were associated with clonal expansion and were present in microglia-like brain macrophages (MLBMs) across multiple brain regions as well as in paired blood samples, indicating a likely hematopoietic origin.
Single-nucleus RNA sequencing from 62 additional AD and control brains showed increased somatic copy number variants (sCNVs) associated with CH in AD MLBMs. Single-cell multi-omic analyses revealed that MLBMs carrying sSNVs and sCNVs display inflammatory and proliferative transcriptional profiles characteristic of disease-associated microglia.
These transcriptional signatures were replicated in induced pluripotent stem cell–derived microglia-like cells engineered to carry TET2, ASXL1, and DNMT3A variants.
Together, the results suggest that clonal somatic driver variants in MLBMs are enriched in Alzheimer’s disease and may promote neuroinflammation and neurodegeneration.