Blume, Tanja; Deussing, Maximilian; Biechele, Gloria; Peters, Finn; Zott, Benedikt; Schmidt, Claudio; Franzmeier, Nicolai; Wind, Karin; Eckenweber, Florian; Sacher, Christian; Shi, Yuan; Ochs, Katharina; Kleinberger, Gernot; Xiang, Xianyuan; Focke, Carola; Lindner, Simon; Gildehaus, Franz-Josef; Beyer, Leonie; von Ungern-Sternberg, Barbara; Bartenstein, Peter; Baumann, Karlheinz; Adelsberger, Helmuth; Rominger, Axel; Cumming, Paul; Willem, Michael; Dorostkar, Mario M.; Herms, Jochen; Brendel, Matthias (2022): Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition. Frontiers in Aging Neuroscience, 14. ISSN 1663-4365
![[thumbnail of fnagi-14-854031.pdf]](https://oa-fund.ub.uni-muenchen.de/style/images/fileicons/text.png)
fnagi-14-854031.pdf
The publication is available under the license Creative Commons Attribution.
Download (7MB)
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.
Doc-Type: | Article (LMU Hospital) |
---|---|
Organisational unit (Faculties): | 07 Medicine > Medical Center of the University of Munich > Clinic and Polyclinic for Nuclear Medicine |
DFG subject classification of scientific disciplines: | Life sciences |
Date Deposited: | 20. Oct 2022 11:33 |
Last Modified: | 07. Dec 2023 12:15 |
URI: | https://oa-fund.ub.uni-muenchen.de/id/eprint/177 |
DFG: | Funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) - 491502892 |