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J Nucl Med. 2019 Apr;60(4):548-554. doi: 10.2967/jnumed.118.217703. Epub 2018 Sep 27.

Early and Longitudinal Microglial Activation but Not Amyloid Accumulation Predicts Cognitive Outcome in PS2APP Mice.

Author information

1
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.
2
Center for Neuropathology and Prion Research, Ludwig-Maximilians-University of Munich, Munich, Germany.
3
Institute of Neuroscience, Technical University of Munich, Munich, Germany.
4
DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.
5
Munich Cluster for Systems Neurology, University of Munich, Munich, Germany.
6
Biomedical Center, Biochemistry, Ludwig-Maximilians-University of Munich, Munich, Germany.
7
Roche Pharma Research and Early Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland; and.
8
Department of Nuclear Medicine, Inselspital, University Hospital Bern, Bern, Switzerland.
9
Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany matthias.brendel@med.uni-muenchen.de.

Abstract

Neuroinflammation may have beneficial or detrimental net effects on the cognitive outcome of Alzheimer disease (AD) patients. PET imaging with 18-kDa translocator protein (TSPO) enables longitudinal monitoring of microglial activation in vivo. Methods: We compiled serial PET measures of TSPO and amyloid with terminal cognitive assessment (water maze) in an AD transgenic mouse model (PS2APP) from 8 to 13 mo of age, followed by immunohistochemical analyses of microglia, amyloid, and synaptic density. Results: Better cognitive outcome and higher synaptic density in PS2APP mice was predicted by higher TSPO expression at 8 mo. The progression of TSPO activation to 13 mo also showed a moderate association with spared cognition, but amyloidosis did not correlate with the cognitive outcome, regardless of the time point. Conclusion: This first PET investigation with longitudinal TSPO and amyloid PET together with terminal cognitive testing in an AD mouse model indicates that continuing microglial response seems to impart preserved cognitive performance.

KEYWORDS:

TSPO PET; amyloid PET; neuroinflammation; synaptic density; water maze

PMID:
30262517
DOI:
10.2967/jnumed.118.217703

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