Microglia, the immune cells that patrol the brain, accumulate mutations in specific cancer-driving genes without ever becoming cancerous - and those mutations may help push the brain toward Alzheimer's disease. That is the central finding of a study from Boston Children's Hospital published in Cell, led by Christopher Walsh, chief of the Division of Genetics and Genomics at Boston Children's and a Howard Hughes Medical Institute investigator, with colleagues Alice Eunjung Lee and August Yue Huang.
The team sequenced 149 known cancer-driver genes in tissue from 190 donated brains of people who had Alzheimer's disease and compared them with 121 brains from people without the disease. The Alzheimer's samples carried more single-letter DNA changes, and the changes clustered repeatedly in the same five cancer-driver genes rather than scattering randomly across the genome. That pattern suggests the mutations are not incidental background noise from aging but are being selected for in particular genes in microglia.
The overlap Walsh describes is with blood cancers specifically. "We find that to some extent, Alzheimer's disease is a little like cancer - driven by the same mutations that drive blood cancers like lymphoma and leukemia," he said. Because oncology already has a deep shelf of drugs aimed at exactly those mutations, he suggests some of them might turn out to be useful against Alzheimer's, which would be a far faster path than developing new compounds from scratch.
Cells throughout the body pick up dozens of mutations a year as a normal consequence of aging, so the interesting question is not whether microglia mutate but which mutations matter and what they do to cell behavior. The researchers say their findings could point toward new diagnostic approaches as well as treatments, though translating a genetic signature in postmortem brain tissue into a test or a therapy for living patients remains work still to be done.