Alzheimer's Disease Features Dialed Down in Mice Missing Methylation-Related Gene

In PLOS Biology, researchers at the Fourth Military Medical University and other centers in China present findings from a mouse model study that found diminished Alzheimer's disease (AD) features in animals missing a methyltransferase enzyme, highlighting the potential importance of m6A RNA methylation in the neurodegenerative condition. By dialing down expression of the methyltransferase-like 3 (METTL3) in monocyte-derived macrophage immune cells, the team initially found that it could ease some of the cognitive symptoms in a mouse model of Alzheimer's disease. Then in a series of follow-up cell line experiments, they demonstrate that the absence of METTL3 kicks off a series of events affecting DNA methyltransferase 3A (DNMT3A) translation, downstream alpha-tubulin modification, and subsequent migration by amyloid beta-clearing macrophage cells via altered m6A methylation. "We found that METTL3 ablation enhances the infiltration of monocyte-derived macrophages in an [amyloid beta-induced Alzheimer's disease] mouse model," the authors report, adding that the findings "suggest that m6A modifications are potential targets for the treatment of AD," the authors report, adding that "upstream regulation of METTL3 in AD remains to be explored in the future."