Early loss of microglial p38α MAPK in the APPswe/PS1dE9 mouse model of Alzheimer’s disease alters soluble amyloid beta and reduces microglia co‐localization with amyloid plaques without affecting amyloid‐associated pathology

摘要: Background The p38 alpha mitogen‐activated protein kinase (p38α) pathway is linked to both innate and adaptive immune responses, and is currently under investigation as a target for drug development in the context of Alzheimer’s disease (AD) and other conditions with neuroinflammatory dysfunction (Asih et al., 2020). Preclinical data indicates that p38α inhibition can protect against AD‐associated neuropathology, although the cellular mechanisms and signaling pathways that underlie these effects have not been fully elucidated. Evidence suggests that inhibition of p38α may provide benefit by modulating microglial‐associated neuroinflammatory processes that contribute to the development of AD pathology. The present study tests this hypothesis by assessing early‐stage pathological changes in AD model mice following microglial‐specific knock out (KO) of p38α. Methods KO of p38α in microglia was …