Nuklearmedizin 2019; 58(02): 144
DOI: 10.1055/s-0039-1683588
Vorträge
Präklinische Bildgebung
Georg Thieme Verlag KG Stuttgart · New York

Chronic PPAR-gamma Agonist Treatment Increases Fibrillar Amyloidosis but Improves Cognition in a Mouse Model of Alzheimer's disease

M Deussing
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
T Blume
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
F Peters
2   Klinikum der Universität München, Zentrum für Neuropathologie und Prionforschung, München
,
B Zott
3   Technische Universität München, Institute of Neuroscience, München
,
C Schmidt
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
Y Shi
2   Klinikum der Universität München, Zentrum für Neuropathologie und Prionforschung, München
,
G Kleinberger
4   Klinikum der Universität München, Biomedical Center (BMC), München
,
C Focke
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
S Lindner
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
FJ Gildehaus
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
L Beyer
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
B von Ungern-Sternberg
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
P Bartenstein
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
K Baumann
5   Roche Innovation Center Basel, Roche Pharmaceutical Research and Early Development, Basel
,
M Dorostkar
2   Klinikum der Universität München, Zentrum für Neuropathologie und Prionforschung, München
,
C Haass
4   Klinikum der Universität München, Biomedical Center (BMC), München
,
H Adelsberger
3   Technische Universität München, Institute of Neuroscience, München
,
A Rominger
6   Inselspital Bern, Universitätsklinik für Nuklearmedizin, Bern
,
J Herms
2   Klinikum der Universität München, Zentrum für Neuropathologie und Prionforschung, München
,
M Brendel
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
› Author Affiliations
Further Information

Publication History

Publication Date:
27 March 2019 (online)

 
 

    Ziel/Aim:

    Immunmodulatory treatment with the PPAR-gamma agonist Pioglitazone shows heterogeneous results in Alzheimer's disease (AD). We aimed to apply longitudinal in-vivo PET monitoring to identify predictive factors for treatment response.

    Methodik/Methods:

    PS2APP (TG) mice and C57Bl/6 (WT) mice were randomly stratified in Pioglitazone (N = 13 TG, N = 8 WT) and placebo treatment (N = 10 TG, N = 7 WT) at the age of 8 months. Therapy was conducted for 5 months. All mice received amyloid-PET (Aß-PET) scans (F-18-Florbetaben) to investigate plaque load and TSPO-PET (F-18-GE180) to analyze microglial activation at baseline and after 5 months. Forebrain PET signals were assessed for each timepoint. Behavioral testing after the terminal PET scan was followed by biochemical and immunohistochemical (IHC) analyses.

    Ergebnisse/Results:

    Pioglitazone treatment resulted in a reduction of -13% (p < 0.001) in the TSPO-PET signal as well as an unexpected increase of Aß-PET in the treatment group compared to placebo (+16% vs. +13%; p < 0.05). Nonetheless, we observed improved cognitive performance and attenuated synaptic loss after treatment. Importantly, we discovered a direct correlation between Aß-PET increase with TSPO decrease (R = 0.62; p < 0.05) and improved cognitive outcome (R = 0.39 p < 0.05). IHC validated PET results and revealed, that dense proportions of the Aß plaque raised during treatment, whereas non fibrillar parts decreased.

    Schlussfolgerungen/Conclusions:

    Reduction of microglial activation by Pioglitazone treatment is associated with consecutive Aß-PET signal increase due to more condensed amyloid plaques and accompanied but ameliorated cognitive performance and attenuated synaptic loss after treatment. This finding has strong implications to Pioglitazone treatment monitoring by Aß-PET as a signal increase over time could be misinterpreted as a treatment failure. Furthermore, this indicates for the first time that increasing fibrillar amyloidosis can preserve cognition.


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