MIT araştırması, bir Alzheimer risk geninin sinir hücrelerinin yalıtımını nasıl zayıflattığını izliyor

APOE4, the gene variant that poses the largest genetic risk for late-onset Alzheimer’s disease, interferes with myelin, the fatty coating that helps neurons carry electrical signals efficiently. A study from MIT’s Picower Institute, published in Cell Stem Cell, ties this damage to a suppressed molecular pathway called Wnt signalling in oligodendrocytes, the cells that supply the coating. When the pathway is weak, these cells store fat as droplets instead of using it to insulate nerve fibres. The team, led by Li-Huei Tsai with first author Leyla Akay, used several methods, including a CRISPR screen that knocked out protein-coding genes one at a time, and found that genes promoting Wnt were less accessible in APOE4 samples than in APOE3 ones. Blocking GSK3b, a protein that suppresses Wnt, reduced the droplets in cultured cells and raised myelination in the hippocampus of mice modelling Alzheimer’s. The results hint that this approach could serve as a proof-of-concept treatment strategy.