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Publication : Relationship Between Reactive Astrocytes, by [(18)F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer's Disease.

First Author  Kong Y Year  2024
Journal  Mol Neurobiol PubMed ID  38502413
Mgi Jnum  J:350687 Mgi Id  MGI:7664334
Doi  10.1007/s12035-024-04106-7 Citation  Kong Y, et al. (2024) Relationship Between Reactive Astrocytes, by [(18)F]SMBT-1 Imaging, with Amyloid-Beta, Tau, Glucose Metabolism, and TSPO in Mouse Models of Alzheimer's Disease. Mol Neurobiol
abstractText  Reactive astrocytes play an important role in the development of Alzheimer's disease (AD). Here, we aimed to investigate the temporospatial relationships among monoamine oxidase-B, tau and amyloid-beta (Abeta), translocator protein, and glucose metabolism by using multitracer imaging in AD transgenic mouse models. Positron emission tomography (PET) imaging with [(18)F]SMBT-1 (monoamine oxidase-B), [(18)F]florbetapir (Abeta), [(18)F]PM-PBB3 (tau), [(18)F]fluorodeoxyglucose (FDG), and [(18)F]DPA-714 (translocator protein) was carried out in 5- and 10-month-old APP/PS1, 11-month-old 3xTg mice, and aged-matched wild-type mice. The brain regional referenced standard uptake value (SUVR) was computed with the cerebellum as the reference region. Immunofluorescence staining was performed on mouse brain tissue slices. [(18)F]SMBT-1 and [(18)F]florbetapir SUVRs were greater in the cortex and hippocampus of 10-month-old APP/PS1 mice than in those of 5-month-old APP/PS1 mice and wild-type mice. No significant difference in the regional [(18)F]FDG or [(18)F]DPA-714 SUVRs was observed in the brains of 5- or 10-month-old APP/PS1 mice or wild-type mice. No significant difference in the SUVRs of any tracer was observed between 11-month-old 3xTg mice and age-matched wild-type mice. A positive correlation between the SUVRs of [(18)F]florbetapir and [(18)F]DPA-714 in the cortex and hippocampus was observed among the transgenic mice. Immunostaining validated the distribution of MAO-B and limited Abeta and tau pathology in 11-month-old 3xTg mice; and Abeta deposits in brain tissue from 10-month-old APP/PS1 mice. In summary, these findings provide in vivo evidence that an increase in astrocyte [(18)F]SMBT-1 accompanies Abeta accumulation in APP/PS1 models of AD amyloidosis.
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