Frontiers in Aging Neuroscience (Mar 2022)
Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
- Tanja Blume,
- Maximilian Deussing,
- Gloria Biechele,
- Finn Peters,
- Benedikt Zott,
- Benedikt Zott,
- Claudio Schmidt,
- Nicolai Franzmeier,
- Karin Wind,
- Karin Wind,
- Florian Eckenweber,
- Christian Sacher,
- Yuan Shi,
- Katharina Ochs,
- Gernot Kleinberger,
- Gernot Kleinberger,
- Xianyuan Xiang,
- Carola Focke,
- Simon Lindner,
- Franz-Josef Gildehaus,
- Leonie Beyer,
- Barbara von Ungern-Sternberg,
- Peter Bartenstein,
- Karlheinz Baumann,
- Helmuth Adelsberger,
- Axel Rominger,
- Axel Rominger,
- Paul Cumming,
- Paul Cumming,
- Michael Willem,
- Mario M. Dorostkar,
- Mario M. Dorostkar,
- Jochen Herms,
- Jochen Herms,
- Jochen Herms,
- Matthias Brendel,
- Matthias Brendel,
- Matthias Brendel
Affiliations
- Tanja Blume
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Maximilian Deussing
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Gloria Biechele
- Department of Radiology, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Finn Peters
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Benedikt Zott
- Institute of Neuroscience, Technical University of Munich, Munich, Germany
- Benedikt Zott
- Department of Diagnostic and Interventional Neuroradiology, Klinikum Rechts der Isar, Technical University of Munich, Munich, Germany
- Claudio Schmidt
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Nicolai Franzmeier
- Institute for Stroke and Dementia Research, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Karin Wind
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Karin Wind
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Florian Eckenweber
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Christian Sacher
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Yuan Shi
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Katharina Ochs
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Gernot Kleinberger
- Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig Maximilian University of Munich, Munich, Germany
- Gernot Kleinberger
- ISAR Bioscience GmbH, Planegg, Germany
- Xianyuan Xiang
- Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig Maximilian University of Munich, Munich, Germany
- Carola Focke
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Simon Lindner
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Franz-Josef Gildehaus
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Leonie Beyer
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Barbara von Ungern-Sternberg
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Peter Bartenstein
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Karlheinz Baumann
- Roche Pharma Research and Early Development, Neuroscience Discovery, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland
- Helmuth Adelsberger
- Department of Radiology, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Axel Rominger
- 0SyNergy, Ludwig Maximilian University of Munich, Munich, Germany
- Axel Rominger
- 1Department of Nuclear Medicine, Inselspital Bern, Bern, Switzerland
- Paul Cumming
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Paul Cumming
- 2School of Psychology and Counselling, Queensland University of Technology, Brisbane, QLD, Australia
- Michael Willem
- Metabolic Biochemistry, Faculty of Medicine, Biomedical Center (BMC), Ludwig Maximilian University of Munich, Munich, Germany
- Mario M. Dorostkar
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Mario M. Dorostkar
- 3Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich, Munich, Germany
- Jochen Herms
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Jochen Herms
- 0SyNergy, Ludwig Maximilian University of Munich, Munich, Germany
- Jochen Herms
- 3Center for Neuropathology and Prion Research, Ludwig Maximilian University of Munich, Munich, Germany
- Matthias Brendel
- DZNE – German Center for Neurodegenerative Diseases, Munich, Germany
- Matthias Brendel
- Department of Nuclear Medicine, University Hospital of Munich, Ludwig Maximilian University of Munich, Munich, Germany
- Matthias Brendel
- 0SyNergy, Ludwig Maximilian University of Munich, Munich, Germany
- DOI
- https://doi.org/10.3389/fnagi.2022.854031
- Journal volume & issue
-
Vol. 14
Abstract
We undertook longitudinal β-amyloid positron emission tomography (Aβ-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone in Aβ model mice. We thus tested the hypothesis this treatment would rescue from increases of the Aβ-PET signal while promoting spatial learning and preservation of synaptic density. Here, we investigated longitudinally for 5 months PS2APP mice (N = 23; baseline age: 8 months) and AppNL–G–F mice (N = 37; baseline age: 5 months) using Aβ-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses. Surprisingly, Aβ-PET and immunohistochemistry revealed a shift toward higher fibrillary composition of Aβ-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity. These translational data suggest that a shift toward higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the Aβ-PET signal upon immunomodulatory treatments targeting Aβ aggregation can thus be protective.
Keywords
