Harvard Medical School: Cancer-Linked Mutations Accumulate in Alzheimer’s Disease Brains

A study has found that cancer-causing genetic mutations accumulate in the brains of patients with Alzheimer’s disease.

A research team led by Christopher Walsh of Harvard Medical School said on the 9th (local time) that it had published a paper in the international journal Cell reporting that cancer-causing gene mutations are abundant in brain immune cells of patients with Alzheimer’s disease and promote inflammation and cell proliferation.

The team conducted whole-genome sequencing on hundreds of brain tissue samples from patients with Alzheimer’s disease and healthy controls. The results showed that somatic mutations in cancer-causing genes were significantly more common in the brains of patients than in those of controls.

The mutations were concentrated in genes associated with clonal hematopoiesis, a phenomenon in which blood cells carrying a particular genetic mutation proliferate and become dominant. The same mutations were also found in patients’ blood, which the team said suggests they likely originated there.

Single-cell analysis showed that the mutations accumulated mainly in “microglia-like brain macrophages,” which resemble microglia, the brain’s resident immune cells. These cells were in a state of active inflammation and proliferation, and their gene expression patterns resembled those of “disease-associated microglia,” which are known to be harmful in Alzheimer’s disease.

The team used stem cell technology to create microglia-like cells carrying mutations in clonal hematopoiesis-related genes such as TET2 and DNMT3A. These cells were easily activated, continuously released inflammatory substances and had a strong capacity to proliferate.

The team said that monitoring clonal hematopoiesis mutations in the blood could be used as a biomarker to predict Alzheimer’s disease risk and could lead to the development of new treatments that eliminate mutated cells or regulate related pathways.