Year: 2022
Type: article
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 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.
Source: Frontiers in Aging Neuroscience
Authors: Tanja Blume, Maximilian Deussing, Gloria Biechele, Finn Peters, Benedikt Zott, Claudio Schmidt, Nicolai Franzmeier, Karin Wind, Florian Eckenweber, Christian Sacher, Yuan Shi, Katharina Ochs, 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, Paul Cumming, Michael Willem, Mario M. Dorostkar, Jochen Herms, Matthias Brendel
Institutions: German Center for Neurodegenerative Diseases, Ludwig-Maximilians-Universität München, TUM Klinikum, Technical University of Munich, Institut für Schlaganfall- und Demenzforschung, F. Hoffmann-La Roche AG, University Hospital of Bern, Munich Cluster for Systems Neurology, Queensland University of Technology, Institut für Neuropathologie
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,827
Funder: Deutsche Forschungsgemeinschaft
Awards: G1523487973, G2370993978
OpenAlex ID: W4220753439