Researchers at Boston Children’s Hospital report that mutations commonly associated with clonal blood-cell expansion and some blood cancers were enriched in microglia-like immune cells in Alzheimer’s brains and were also detectable in matched blood samples. The Cell study proposes that age- or injury-related weakening of the blood-brain barrier could allow mutated blood immune cells to enter the brain, potentially amplifying inflammation and contributing to neurodegeneration.
Scientists from Boston Children’s Hospital report evidence that genetic mutations often seen in clonal hematopoiesis—a common, age-related expansion of mutated blood-cell clones that can increase the risk of some blood cancers—are also found in brain immune cells in people with Alzheimer’s disease.
In the study, published in Cell, the team said it analyzed a targeted set of 149 cancer-driving genes in postmortem brain tissue from 190 people with Alzheimer’s disease and 121 people without the disease. The Alzheimer’s samples showed more single-letter DNA changes than controls, with recurring alterations concentrated in five cancer driver genes, the researchers reported.
The mutations were detected in microglia-like brain immune cells. Because the same types of mutations are commonly associated with blood cancers, the researchers also examined blood samples from the same Alzheimer’s patients and reported finding matching cancer-associated mutations there as well.
The work was led by Christopher Walsh, chief of the Division of Genetics and Genomics at Boston Children’s Hospital. In the hospital’s release, Walsh said the team’s data suggest that “to some extent, Alzheimer’s disease is a little like cancer,” in that it may be driven in part by some of the same mutations implicated in blood cancers such as lymphoma and leukemia.
As a proposed mechanism, the researchers suggested that aging or injury may weaken the blood-brain barrier, allowing immune cells from the bloodstream that carry these mutations to enter the brain and adopt microglia-like features. The study further argues that these mutated cells may skew toward inflammatory and proliferative states, potentially creating a more damaging environment for neurons.
The findings also point to a potential diagnostic angle: because brain tissue is difficult to access in living patients, the researchers said blood-based genetic screening could eventually be explored to assess whether people carry mutations that may be linked to Alzheimer’s risk. In the same release, the team also referenced follow-up work posted as a bioRxiv preprint suggesting that cancer driver mutations detected in blood were associated with Alzheimer’s risk independently of APOE4, a well-established genetic risk factor.
The authors emphasized that the study describes a potential disease mechanism and possible screening approach, not a clinical test or treatment. The research involved collaborators including the Icahn School of Medicine at Mount Sinai and reported funding from the Howard Hughes Medical Institute, the National Institute on Aging, and other sources.
