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@ARTICLE{Endepols:163758,
      author       = {Endepols, Heike and Anglada-Huguet, Marta and Mandelkow,
                      Eckhard and Schmidt, Yannick and Krapf, Philipp and
                      Zlatopolskiy, Boris D and Neumaier, Bernd and Mandelkow, Eva
                      Maria and Drzezga, Alexander},
      title        = {{A}ssessment of the {I}n {V}ivo {R}elationship {B}etween
                      {C}erebral {H}ypometabolism, {T}au {D}eposition, {TSPO}
                      {E}xpression, and {S}ynaptic {D}ensity in a {T}auopathy
                      {M}ouse {M}odel: a {M}ulti-tracer {PET} {S}tudy.},
      journal      = {Molecular neurobiology},
      volume       = {59},
      issn         = {0893-7648},
      address      = {Totowa, NJ},
      publisher    = {Humana Press},
      reportid     = {DZNE-2022-00497},
      pages        = {3402-3413},
      year         = {2022},
      note         = {(CC BY 4.0)},
      abstract     = {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.},
      keywords     = {Alzheimer Disease: diagnostic imaging / Alzheimer Disease:
                      metabolism / Animals / Brain: diagnostic imaging / Brain:
                      metabolism / Disease Models, Animal / Glucose / Humans /
                      Mice / Mice, Transgenic / Positron-Emission Tomography:
                      methods / Receptors, GABA: metabolism / Reproducibility of
                      Results / Tauopathies: diagnostic imaging / Tauopathies:
                      metabolism / tau Proteins: metabolism / Alzheimer’s
                      disease (Other) / Cerebral hypometabolism (Other) /
                      Microglial activation (Other) / Neuroinflammation (Other) /
                      Small animal PET (Other) / Synaptic density (Other) / Tau
                      (Other)},
      cin          = {AG Mandelkow 1 / AG Mandelkow 2},
      ddc          = {570},
      cid          = {I:(DE-2719)1013014 / I:(DE-2719)1013015},
      pnm          = {352 - Disease Mechanisms (POF4-352) / 353 - Clinical and
                      Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-352 / G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9148291},
      pubmed       = {pmid:35312967},
      doi          = {10.1007/s12035-022-02793-8},
      url          = {https://pub.dzne.de/record/163758},
}