Nuklearmedizin 2019; 58(02): 160-161
DOI: 10.1055/s-0039-1683638
Poster
Präklinische Bildgebung
Georg Thieme Verlag KG Stuttgart · New York

Longitudinal PET Monitoring of Microglial Activation in Tau Transgenic P301S Mice Predicts Cognitive Deterioration and Metabolic Decline

M Deussing
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
F Eckenweber
2   Klinikum der Universität München, Universitätsklinik für Nuklearmedizin, München
,
T Blume
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
J Luque
3   Klinikum der Universität München, Zentrum für Neuropathologie und Prionforschung, München
,
C Sacher
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
S Lindner
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
,
M Unterrainer
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
NL Albert
4   Klinikum der Universität München, Klinik für Nuklearmedizin, München
,
A Zwergal
5   Klinikum der Universität München, Klinik und Poliklinik für Neurologie, München
,
P Bartenstein
1   Klinikum der Universität München, Klinik und Poliklinik für Nuklearmedizin, München
,
A Rominger
6   Inselspital Bern, Universitätsklinik für Nuklearmedizin, Bern
,
G Höglinger
7   Deutsches Zentrum für Neurodegenerative Erkrankungen, München
,
J Herms
3   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)

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Ziel/Aim:

The P301 s tau mouse model is known to show age-dependent accumulation of neurofibrillary tangles in brainstem, hippocampus, and neocortex, leading to neuronal loss and cognitive deterioration. However, the role of neuroinflammation in tau mouse models was only sparsely investigated so far. Therefore, we analyzed longitudinal microglial activation by 18kDa translocator protein (TSPO) PET imaging, together with terminal testing of cognitive capabilities and glucose metabolism.

Methodik/Methods:

Transgenic P301S (N = 51) and wild-type (WT, N = 18) mice were imaged with F-18-GE180 (TSPO ligand) at the age of 2 and 6 months. An additional F18-FDG PET scan and behavioral testing in Morris water maze (MWM) were conducted at the age of 6 months. PET-Data analyses were performed by calculating VOI-based regional SUVR in brainstem and hippocampus. Immunohistochemistry served for validation of PET results.

Ergebnisse/Results:

TSPO activity in the brainstem of P301S mice increased from 2 to 6 months and was significantly higher when compared to WT at 6 months (+12%; p < 0.001). In the Hippocampus though we monitored opposite results of TSPO activity, with a peak at 2 months when compared to WT (+3.1%; p < 0.001) and decrease even below WT levels at 6 months of age. Importantly, early TSPO activation in the hippocampus was correlated with worse performance in terminal MWM (R = 0.35; p < 0.05) and with FDG-PET decrease at 6 months of age (R =-0.34; p < 0.01).

Schlussfolgerungen/Conclusions:

Neuroinflammation in the brain stem of P301S tau transgenic mice shows continuous time dependent progression, whereas the peak of hippocampal neuroinflammation occurs early and decreases with aging. Early TSPO activation in this tau mouse model predicts stronger cognitive worsening and more severe metabolic decline, which is opposite to earlier findings of amyloid transgenic mice. Microglial response to protein deposition may have different roles in amyloid and tauopathies.