| First Author | Srinivasan S | Year | 2024 |
| Journal | Front Immunol | Volume | 15 |
| Pages | 1323409 | PubMed ID | 38352874 |
| Mgi Jnum | J:350738 | Mgi Id | MGI:7594541 |
| Doi | 10.3389/fimmu.2024.1323409 | Citation | Srinivasan S, et al. (2024) Inflammasome signaling is dispensable for ss-amyloid-induced neuropathology in preclinical models of Alzheimer's disease. Front Immunol 15:1323409 |
| abstractText | BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disorder affecting memory and cognition. The disease is accompanied by an abnormal deposition of ss-amyloid plaques in the brain that contributes to neurodegeneration and is known to induce glial inflammation. Studies in the APP/PS1 mouse model of ss-amyloid-induced neuropathology have suggested a role for inflammasome activation in ss-amyloid-induced neuroinflammation and neuropathology. METHODS: Here, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ss-amyloid-induced AD neuropathology. RESULTS: Microglia-specific deletion of the inflammasome regulator A20 and inflammasome effector protease caspase-1 in the App(NL-G-F) and APP/PS1 models failed to identify a prominent role for microglial inflammasome signalling in ss-amyloid-induced neuropathology. Moreover, global inflammasome inactivation through respectively full body deletion of caspases 1 and 11 in App(NL-G-F) mice and Nlrp3 deletion in APP/PS1 mice also failed to modulate amyloid pathology and disease progression. In agreement, single-cell RNA sequencing did not reveal an important role for Nlrp3 signalling in driving microglial activation and the transition into disease-associated states, both during homeostasis and upon amyloid pathology. CONCLUSION: Collectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation. |
