Boston Children's Hospital study in Cell finds blood cancer driver mutations enriched in Alzheimer's brains, fueling inflammatory microglia
A blood test might one day flag who is most at risk of Alzheimer's. Researchers at Boston Children's Hospital report in Cell that the same mutations driving blood cancers like leukemia turn up in the brain's immune cells in Alzheimer's, fueling inflammation that damages neurons.
A discovery published this month could reshape how doctors think about who develops Alzheimer's and why. Researchers at Boston Children's Hospital, writing in the journal Cell, report that some of the same genetic mutations that drive blood cancers also appear in the brains of people with Alzheimer's disease. The team carried out deep sequencing of 311 brain samples. They found that somatic mutations in cancer-driver genes, particularly those associated with clonal hematopoiesis, were enriched in Alzheimer's brains compared with healthy ones. Clonal hematopoiesis is a process in which blood stem cells acquire mutations and produce populations of altered immune cells as people age. In the brain, these mutations appear to affect microglia, the resident immune cells that normally help clear debris and protect neurons. The mutated microglia shift into a more inflammatory and proliferative state. That altered behavior creates a damaging environment in which nearby neurons can be harmed and die, contributing to the progression of the disease. The researchers also sequenced blood samples from people with Alzheimer's and found the same cancer mutations present in their blood cells, not just their brains. That overlap points to a possible practical application: blood-based genetic screens that test whether a person carries these mutations and may face higher Alzheimer's risk. The lead researcher, Dr. Christopher Walsh, described Alzheimer's as in some respects behaving a little like cancer, driven by the same mutations that drive lymphoma and leukemia.