Frontiers in Immunology (Jan 2024)
Inflammasome signaling is dispensable for ß-amyloid-induced neuropathology in preclinical models of Alzheimer’s disease
- Sahana Srinivasan,
- Sahana Srinivasan,
- Daliya Kancheva,
- Sofie De Ren,
- Takashi Saito,
- Takashi Saito,
- Takashi Saito,
- Maude Jans,
- Maude Jans,
- Fleur Boone,
- Fleur Boone,
- Charysse Vandendriessche,
- Charysse Vandendriessche,
- Ine Paesmans,
- Hervé Maurin,
- Roosmarijn E. Vandenbroucke,
- Roosmarijn E. Vandenbroucke,
- Esther Hoste,
- Esther Hoste,
- Sofie Voet,
- Sofie Voet,
- Isabelle Scheyltjens,
- Benjamin Pavie,
- Benjamin Pavie,
- Saskia Lippens,
- Saskia Lippens,
- Marius Schwabenland,
- Marco Prinz,
- Marco Prinz,
- Marco Prinz,
- Takaomi Saido,
- Astrid Bottelbergs,
- Kiavash Movahedi,
- Mohamed Lamkanfi,
- Geert van Loo,
- Geert van Loo
Affiliations
- Sahana Srinivasan
- VIB Center for Inflammation Research, Ghent, Belgium
- Sahana Srinivasan
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Daliya Kancheva
- Brain and Systems Immunology Lab, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium
- Sofie De Ren
- Neuroscience Therapeutic Area, Janssen Research and Development, Beerse, Belgium
- Takashi Saito
- Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan
- Takashi Saito
- Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan
- Takashi Saito
- Department of Neuroscience and Pathobiology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Aichi, Japan
- Maude Jans
- VIB Center for Inflammation Research, Ghent, Belgium
- Maude Jans
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Fleur Boone
- VIB Center for Inflammation Research, Ghent, Belgium
- Fleur Boone
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Charysse Vandendriessche
- VIB Center for Inflammation Research, Ghent, Belgium
- Charysse Vandendriessche
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Ine Paesmans
- Neuroscience Therapeutic Area, Janssen Research and Development, Beerse, Belgium
- Hervé Maurin
- Neuroscience Therapeutic Area, Janssen Research and Development, Beerse, Belgium
- Roosmarijn E. Vandenbroucke
- VIB Center for Inflammation Research, Ghent, Belgium
- Roosmarijn E. Vandenbroucke
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Esther Hoste
- VIB Center for Inflammation Research, Ghent, Belgium
- Esther Hoste
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Sofie Voet
- VIB Center for Inflammation Research, Ghent, Belgium
- Sofie Voet
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- Isabelle Scheyltjens
- Brain and Systems Immunology Lab, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium
- Benjamin Pavie
- VIB Center for Inflammation Research, Ghent, Belgium
- Benjamin Pavie
- VIB Bioimaging Core, Ghent, Belgium
- Saskia Lippens
- VIB Center for Inflammation Research, Ghent, Belgium
- Saskia Lippens
- VIB Bioimaging Core, Ghent, Belgium
- Marius Schwabenland
- Institute of Neuropathology Medical Center, University of Freiburg, Freiburg, Germany
- Marco Prinz
- Institute of Neuropathology Medical Center, University of Freiburg, Freiburg, Germany
- Marco Prinz
- 0Signalling Research Centres BIOSS and CIBSS, University of Freiburg, Freiburg, Germany
- Marco Prinz
- 1Center for Basics in NeuroModulation (NeuroModulBasics), Faculty of Medicine, University of Freiburg, Freiburg, Germany
- Takaomi Saido
- Laboratory for Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama, Japan
- Astrid Bottelbergs
- Neuroscience Therapeutic Area, Janssen Research and Development, Beerse, Belgium
- Kiavash Movahedi
- Brain and Systems Immunology Lab, Brussels Center for Immunology, Vrije Universiteit Brussel, Brussels, Belgium
- Mohamed Lamkanfi
- 2Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium
- Geert van Loo
- VIB Center for Inflammation Research, Ghent, Belgium
- Geert van Loo
- Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium
- DOI
- https://doi.org/10.3389/fimmu.2024.1323409
- Journal volume & issue
-
Vol. 15
Abstract
BackgroundAlzheimer’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.MethodsHere, we evaluated the in vivo role of microglia-selective and full body inflammasome signalling in several mouse models of ß-amyloid-induced AD neuropathology.ResultsMicroglia-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.ConclusionCollectively, these results question a generalizable role for inflammasome activation in preclinical amyloid-only models of neuroinflammation.
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