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000163758 041__ $$aEnglish
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000163758 1001_ $$00000-0002-6166-4818$$aEndepols, Heike$$b0
000163758 245__ $$aAssessment of the In Vivo Relationship Between Cerebral Hypometabolism, Tau Deposition, TSPO Expression, and Synaptic Density in a Tauopathy Mouse Model: a Multi-tracer PET Study.
000163758 260__ $$aTotowa, NJ$$bHumana Press$$c2022
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000163758 520__ $$aCerebral 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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000163758 650_7 $$2Other$$aAlzheimer’s disease
000163758 650_7 $$2Other$$aCerebral hypometabolism
000163758 650_7 $$2Other$$aMicroglial activation
000163758 650_7 $$2Other$$aNeuroinflammation
000163758 650_7 $$2Other$$aSmall animal PET
000163758 650_7 $$2Other$$aSynaptic density
000163758 650_7 $$2Other$$aTau
000163758 650_2 $$2MeSH$$aAlzheimer Disease: diagnostic imaging
000163758 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000163758 650_2 $$2MeSH$$aAnimals
000163758 650_2 $$2MeSH$$aBrain: diagnostic imaging
000163758 650_2 $$2MeSH$$aBrain: metabolism
000163758 650_2 $$2MeSH$$aDisease Models, Animal
000163758 650_2 $$2MeSH$$aGlucose
000163758 650_2 $$2MeSH$$aHumans
000163758 650_2 $$2MeSH$$aMice
000163758 650_2 $$2MeSH$$aMice, Transgenic
000163758 650_2 $$2MeSH$$aPositron-Emission Tomography: methods
000163758 650_2 $$2MeSH$$aReceptors, GABA: metabolism
000163758 650_2 $$2MeSH$$aReproducibility of Results
000163758 650_2 $$2MeSH$$aTauopathies: diagnostic imaging
000163758 650_2 $$2MeSH$$aTauopathies: metabolism
000163758 650_2 $$2MeSH$$atau Proteins: metabolism
000163758 7001_ $$0P:(DE-2719)9000008$$aAnglada-Huguet, Marta$$b1$$udzne
000163758 7001_ $$0P:(DE-2719)2541671$$aMandelkow, Eckhard$$b2$$udzne
000163758 7001_ $$00000-0002-7976-2205$$aSchmidt, Yannick$$b3
000163758 7001_ $$00000-0003-1671-2443$$aKrapf, Philipp$$b4
000163758 7001_ $$00000-0001-5818-1260$$aZlatopolskiy, Boris D$$b5
000163758 7001_ $$00000-0001-5425-3116$$aNeumaier, Bernd$$b6
000163758 7001_ $$0P:(DE-2719)2541658$$aMandelkow, Eva Maria$$b7$$udzne
000163758 7001_ $$0P:(DE-2719)2811239$$aDrzezga, Alexander$$b8$$udzne
000163758 773__ $$0PERI:(DE-600)2079384-4$$a10.1007/s12035-022-02793-8$$p3402-3413$$tMolecular neurobiology$$v59$$x0893-7648$$y2022
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