Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition.

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; ... (2022). Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition. Frontiers in aging neuroscience, 14, p. 854031. Frontiers Research Foundation 10.3389/fnagi.2022.854031

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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 App NL-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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Radiology, Neuroradiology and Nuclear Medicine (DRNN) > Clinic of Nuclear Medicine

UniBE Contributor:

Rominger, Axel Oliver

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1663-4365

Publisher:

Frontiers Research Foundation

Language:

English

Submitter:

Pubmed Import

Date Deposited:

19 Apr 2022 15:08

Last Modified:

24 Apr 2022 02:00

Publisher DOI:

10.3389/fnagi.2022.854031

PubMed ID:

35431893

Uncontrolled Keywords:

AppNL–G–F mice Aβ-PET Aβ-plaque composition PS2APP mice microglia pioglitazone

BORIS DOI:

10.48350/169355

URI:

https://boris.unibe.ch/id/eprint/169355

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