Details

Autor(en) / Beteiligte

• 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
• van Loo, Geert

Titel

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

Ist Teil von

• Frontiers in immunology, 2024, Vol.15, p.1323409-1323409

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 mouse model of ß-amyloid-induced neuropathology have suggested a role for inflammasome activation in ß-amyloid-induced neuroinflammation and neuropathology. Here, we evaluated the role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology. Microglia-specific deletion of the inflammasome regulator A20 and inflammasome effector protease caspase-1 in the and 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 mice and Nlrp3 deletion in 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. Collectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation.