| First Author | Heneka MT | Year | 2013 |
| Journal | Nature | Volume | 493 |
| Issue | 7434 | Pages | 674-8 |
| PubMed ID | 23254930 | Mgi Jnum | J:194405 |
| Mgi Id | MGI:5473734 | Doi | 10.1038/nature11729 |
| Citation | Heneka MT, et al. (2013) NLRP3 is activated in Alzheimer's disease and contributes to pathology in APP/PS1 mice. Nature 493(7434):674-8 |
| abstractText | Alzheimer's disease is the world's most common dementing illness. Deposition of amyloid-beta peptide drives cerebral neuroinflammation by activating microglia. Indeed, amyloid-beta activation of the NLRP3 inflammasome in microglia is fundamental for interleukin-1beta maturation and subsequent inflammatory events. However, it remains unknown whether NLRP3 activation contributes to Alzheimer's disease in vivo. Here we demonstrate strongly enhanced active caspase-1 expression in human mild cognitive impairment and brains with Alzheimer's disease, suggesting a role for the inflammasome in this neurodegenerative disease. Nlrp3(-/-) or Casp1(-/-) mice carrying mutations associated with familial Alzheimer's disease were largely protected from loss of spatial memory and other sequelae associated with Alzheimer's disease, and demonstrated reduced brain caspase-1 and interleukin-1beta activation as well as enhanced amyloid-beta clearance. Furthermore, NLRP3 inflammasome deficiency skewed microglial cells to an M2 phenotype and resulted in the decreased deposition of amyloid-beta in the APP/PS1 model of Alzheimer's disease. These results show an important role for the NLRP3/caspase-1 axis in the pathogenesis of Alzheimer's disease, and suggest that NLRP3 inflammasome inhibition represents a new therapeutic intervention for the disease. |
