Epidemiological studies have linked uric acid (UA), the end product of purine metabolism in humans, with reduced Alzheimer's disease (AD) risk. We found decreased serum UA levels in AD patients versus age-matched controls, while upstream purine metabolites remained unchanged. In 5XFAD mice, UA supplementation for two months improved cognitive function and decreased amyloid plaque burden. Mechanistically, UA enhanced microglial b-amyloid (Abeita) phagocytosis and induced transcriptional reprogramming in AD mouse microglia, characterized by upregulated phagocytic pathways and reduced immune responses. UA treatment restored the recycling of Abeita receptors CD36 and TREM2 in microglia, enhanced lysosomal biogenesis, and facilitated Abeita degradation. These findings identify UA as a critical modulator of microglial Abeita processing and suggest exploring low-dose UA supplementation as a therapeutic strategy for AD.
谢德 (Thu,) studied this question.