Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer’s disease

Abstract: 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 AppNL-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 AppNL-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

Angaben zum Objekt

• Standort: Deutsche Nationalbibliothek Frankfurt am Main
• Umfang: Online-Ressource
• Sprache: Englisch
• Anmerkungen: Frontiers in immunology. - 15 (2024) , 1323409, ISSN: 1664-3224

Beteiligte, Orts- und Zeitangaben

• Ereignis: Veröffentlichung
• (wo): Freiburg
• (wer): Universität
• (wann): 2024
• Urheber: Srinivasan, Sahana ; Kancheva, Daliya ; De Ren, Sofie ; Saito, Takashi ; Jans, Maude ; Boone, Fleur ; Vandendriessche, Charysse ; Paesmans, Ine ; Maurin, Hervé ; Vandenbroucke, Roosmarijn E. ; Hoste, Esther ; Voet, Sofie ; Scheyltjens, Isabelle ; Pavie, Benjamin ; Lippens, Saskia ; Schwabenland, Marius ; Prinz, Marco ; Saido, Takaomi ; Bottelbergs, Astrid ; Movahedi, Kiavash ; Lamkanfi, Mohamed ; Loo, Geert van

Weitere Informationen

• DOI: 10.3389/fimmu.2024.1323409
• URN: urn:nbn:de:bsz:25-freidok-2457300
• Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Letzte Aktualisierung: 14.08.2025, 10:54 MESZ