A recent study published in Cell Stem Cell indicates that certain mutations in blood stem cells could offer protection against late-onset Alzheimer's disease. The research, led by Baylor College of Medicine, found that individuals and mice with blood stem cell mutations in the TET2 gene, but not in DNMT3A, had a lower risk of developing Alzheimer’s.
Dr. Katherine King, professor of pediatrics at Baylor and part of Texas Children’s Hospital, explained the significance of hematopoietic stem cells: "Our lab has long been studying blood stem cells, also called hematopoietic stem cells." These cells are crucial for generating various blood types necessary for health. With age, these stem cells can mutate; about 20% of 70-year-olds experience this phenomenon. While often harmless, some mutations lead to clonal hematopoiesis—a process linked to cardiovascular diseases and other conditions. However, its connection to Alzheimer's remained unclear until now.
Dr. Katie A. Matatall from King's lab stated: “In the current study, we investigated the effect of the two genes most commonly mutated in clonal hematopoiesis, TET2 and DNMT3A, on Alzheimer’s disease.” Using data from the UK Biobank and a mouse model of Alzheimer’s disease, researchers assessed how these mutations affect Alzheimer's prevalence.
The results showed a distinct difference between the two gene mutations. TET2-mutant clonal hematopoiesis correlated with a 47% reduced risk of late-onset Alzheimer’s in humans. In mice models, Tet2-mutant bone marrow transplants lessened cognitive decline and beta-amyloid plaque formation—effects absent with Dnmt3a-mutant cells.
Matatall added: “Furthermore, we found that the protective effect seemed to be mediated by TET2-clonal stem cells circulating in the blood.” These immune cells were more effective at migrating into the brain and clearing beta-amyloid deposits than non-mutated counterparts.
King emphasized the novelty of these findings: “Until now clonal hematopoiesis has primarily been associated with promoting the progression of disease... We need to think about clonal hematopoiesis in a mutation-specific way and assess their risks and benefits.”
This research provides a new platform for exploring how clonal hematopoiesis influences Alzheimer’s disease and may guide future strategies for managing central nervous system degenerative diseases.
