Cancer-linked mutations in the brain cells may drive Alzheimer’s disease

As the body ages, cells naturally accumulate dozens of genetic mutations each year. New research from Boston Children's Hospital, published in Cell, finds that the brain's resident immune cells, microglia, amass mutations in specific cancer-driving genes yet they don't manifest as cancer. Instead, these mutations may help drive Alzheimer's disease.

The research team, led by Christopher Walsh, MD, PhD, Chief of the Division of Genetics and Genomics at Boston Children's and an Investigator of the Howard Hughes Medical Institute, and collaborators Alice Eunjung Lee, PhD, and August Yue Huang, PhD, also in the Division of Genetics and Genomics, all Professors at Harvard Medical School and Associate Members of the Broad Institute of MIT and Harvard, say their study findings may provide insights into new Alzheimer's disease diagnostics and treatments.

"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," said Walsh. "This is helpful because we have a lot of drugs to fight cancer and some of them might be useful therapeutically for Alzheimer's disease."

For the new study, the research team sequenced 149 cancer-driving genes from tissue samples in 190 brains donated from people with Alzheimer's disease compared to 121 healthy brains. The Alzheimer's samples had more single DNA letter changes than the healthy tissue with the most changes found repeatedly in the same five cancer driver genes, meaning the microglia were amassing mutations in specific genes.