Scientists Discover Gene Signature for Plaque-Eating Microglia in Alzheimer's Disease

A study in Nature Communications analyzed the mechanisms of microglia that consume amyloid plaques in Alzheimer's disease as a potential channel for therapeutic intervention, reports ScienceDaily . The researchers investigated differences in gene expression underpinning microglia's ability to ingest particles and identified associated regulatory molecules. Microglia that have not ingested amyloid possess gene expression patterns most similar to aged microglia, which are known to be dysfunctional and a major factor in Alzheimer's disease pathogenesis. Furthermore, microglia that engulf the plaques associated with Alzheimer's disease develop a characteristic gene expression signature partly induced by a gene called Hif1a. This boosts the ability of microglia to consume proteins such as amyloid, while lowering Hif1a concentrations has the opposite effect. "This relationship between Hif1a and cognitive decline in Alzheimer's disease is yet to be comprehensively uncovered," explained Duke-National University of Singapore Medical School Ph.D student Gabriel Chew. "Future work could focus on using gene editing tool CRISPR to test the impact of manipulating Hif1a on symptom severity and disease progression."