NLRP3 is activated in Alzheimer´s disease and contributes to pathology in APP/PS1 mice

摘要: Alzheimer's disease is the world's most common dementing illness. Deposition of amyloid-β peptide drives cerebral neuroinflammation by activating microglia. Indeed, activation NLRP3 inflammasome in microglia fundamental for interleukin-1β maturation and subsequent inflammatory events. However, it remains unknown whether contributes to vivo. Here we demonstrate strongly enhanced active caspase-1 expression human mild cognitive impairment brains with disease, suggesting a role this neurodegenerative disease. Nlrp3(-/-) or Casp1(-/-) mice carrying mutations associated familial were largely protected from loss spatial memory other sequelae demonstrated reduced brain as well clearance. Furthermore, deficiency skewed microglial cells an M2 phenotype resulted decreased deposition APP/PS1 model These results show important NLRP3/caspase-1 axis pathogenesis suggest that inhibition represents new therapeutic intervention