Home > Publications Database > 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. > print

001     163758
005     20240612120602.0
024 7 _ |a pmc:PMC9148291
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024 7 _ |a 10.1007/s12035-022-02793-8
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024 7 _ |a 0893-7648
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024 7 _ |a 1559-1182
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037 _ _ |a DZNE-2022-00497
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Endepols, Heike
|0 0000-0002-6166-4818
|b 0
245 _ _ |a 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.
260 _ _ |a Totowa, NJ
|c 2022
|b Humana Press
336 7 _ |a article
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500 _ _ |a (CC BY 4.0)
520 _ _ |a 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.
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650 _ 7 |a Alzheimer’s disease
|2 Other
650 _ 7 |a Cerebral hypometabolism
|2 Other
650 _ 7 |a Microglial activation
|2 Other
650 _ 7 |a Neuroinflammation
|2 Other
650 _ 7 |a Small animal PET
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650 _ 7 |a Synaptic density
|2 Other
650 _ 7 |a Tau
|2 Other
650 _ 2 |a Alzheimer Disease: diagnostic imaging
|2 MeSH
650 _ 2 |a Alzheimer Disease: metabolism
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Brain: diagnostic imaging
|2 MeSH
650 _ 2 |a Brain: metabolism
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Glucose
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Transgenic
|2 MeSH
650 _ 2 |a Positron-Emission Tomography: methods
|2 MeSH
650 _ 2 |a Receptors, GABA: metabolism
|2 MeSH
650 _ 2 |a Reproducibility of Results
|2 MeSH
650 _ 2 |a Tauopathies: diagnostic imaging
|2 MeSH
650 _ 2 |a Tauopathies: metabolism
|2 MeSH
650 _ 2 |a tau Proteins: metabolism
|2 MeSH
700 1 _ |a Anglada-Huguet, Marta
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700 1 _ |a Mandelkow, Eckhard
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700 1 _ |a Schmidt, Yannick
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700 1 _ |a Krapf, Philipp
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700 1 _ |a Zlatopolskiy, Boris D
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700 1 _ |a Neumaier, Bernd
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700 1 _ |a Mandelkow, Eva Maria
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700 1 _ |a Drzezga, Alexander
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773 _ _ |a 10.1007/s12035-022-02793-8
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|t Molecular neurobiology
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