Somatic Cancer Variants Enriched In Alzheimer’S Disease Microglia-Like Cells Drive Inflammatory And Proliferative States
Recent research sheds light on a surprising connection between genetic changes typically associated with cancer and the progression of Alzheimer’s disease. It turns out that the brain’s own immune cells, called microglia, can accumulate specific DNA alterations, known as somatic mutations, as we age. These aren’t inherited mutations but rather changes that occur in individual cells after conception.
In people with Alzheimer’s, these somatic mutations are found to be particularly enriched in microglia-like cells. What’s more, these specific mutations often occur in genes known as “cancer driver genes” – genes that, when altered, can promote uncontrolled cell growth. The presence of these mutations appears to push the microglia into an “inflammatory” state, meaning they contribute to harmful inflammation in the brain, and a “proliferative” state, causing them to multiply rapidly.
This phenomenon is linked to something called clonal hematopoiesis, where a single mutated blood stem cell gives rise to a large number of identical blood cells. The findings suggest that these mutated microglia, which may even originate from blood-forming cells, could be a significant factor in driving the neuroinflammation and neurodegeneration (the progressive loss of brain cells) characteristic of Alzheimer’s disease. Understanding this link could open new avenues for diagnosing and treating this devastating condition.
Source: link to paper