TY  - JOUR
AU  - Endepols, Heike
AU  - Anglada-Huguet, Marta
AU  - Mandelkow, Eckhard
AU  - Schmidt, Yannick
AU  - Krapf, Philipp
AU  - Zlatopolskiy, Boris D
AU  - Neumaier, Bernd
AU  - Mandelkow, Eva Maria
AU  - Drzezga, Alexander
TI  - Assessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study.
JO  - Molecular neurobiology
VL  - 59
SN  - 0893-7648
CY  - Totowa, NJ
PB  - Humana Press
M1  - DZNE-2022-00497
SP  - 3402-3413
PY  - 2022
N1  - (CC BY 4.0)
AB  - Cerebral glucose hypometabolism is a typical hallmark of Alzheimer's disease (AD), usually associated with ongoing neurodegeneration and neuronal dysfunction. However, underlying pathological processes are not fully understood and reproducibility in animal models is not well established. The aim of the present study was to investigate the regional interrelation of glucose hypometabolism measured by [18F]FDG positron emission tomography (PET) with various molecular targets of AD pathophysiology using the PET tracers [18F]PI-2620 for tau deposition, [18F]DPA-714 for TSPO expression associated with neuroinflammation, and [18F]UCB-H for synaptic density in a transgenic tauopathy mouse model. Seven-month-old rTg4510 mice (n = 8) and non-transgenic littermates (n = 8) were examined in a small animal PET scanner with the tracers listed above. Hypometabolism was observed throughout the forebrain of rTg4510 mice. Tau pathology, increased TSPO expression, and synaptic loss were co-localized in the cortex and hippocampus and correlated with hypometabolism. In the thalamus, however, hypometabolism occurred in the absence of tau-related pathology. Thus, cerebral hypometabolism was associated with two regionally distinct forms of molecular pathology: (1) characteristic neuropathology of the Alzheimer-type including synaptic degeneration and neuroinflammation co-localized with tau deposition in the cerebral cortex, and (2) pathological changes in the thalamus in the absence of other markers of AD pathophysiology, possibly reflecting downstream or remote adaptive processes which may affect functional connectivity. Our study demonstrates the feasibility of a multitracer approach to explore complex interactions of distinct AD-pathomechanisms in vivo in a small animal model. The observations demonstrate that multiple, spatially heterogeneous pathomechanisms can contribute to hypometabolism observed in AD mouse models and they motivate future longitudinal studies as well as the investigation of possibly comparable pathomechanisms in human patients.
KW  - Alzheimer Disease: diagnostic imaging
KW  - Alzheimer Disease: metabolism
KW  - Animals
KW  - Brain: diagnostic imaging
KW  - Brain: metabolism
KW  - Disease Models, Animal
KW  - Glucose
KW  - Humans
KW  - Mice
KW  - Mice, Transgenic
KW  - Positron-Emission Tomography: methods
KW  - Receptors, GABA: metabolism
KW  - Reproducibility of Results
KW  - Tauopathies: diagnostic imaging
KW  - Tauopathies: metabolism
KW  - tau Proteins: metabolism
KW  - Alzheimer’s disease (Other)
KW  - Cerebral hypometabolism (Other)
KW  - Microglial activation (Other)
KW  - Neuroinflammation (Other)
KW  - Small animal PET (Other)
KW  - Synaptic density (Other)
KW  - Tau (Other)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC9148291
C6  - pmid:35312967
DO  - DOI:10.1007/s12035-022-02793-8
UR  - https://pub.dzne.de/record/163758
ER  -