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• W2131433223 abstract "Microglial activation is intimately associated with Alzheimer's disease (AD), however its exact role in AD is unknown. Positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO), a biomarker of microglial activation, could enhance our understanding of the in vivo role of microglia in AD, and might serve as a marker of AD progression and treatment response. We aim to evaluate a TSPO-specific radioligand [18 F]PBR06 for visualizing alterations in TSPO and microglial activation in a transgenic mouse model of AD, Thy1-hAPP Lond/Swe (APP L/S). APP L/S mice (n=5) and wild-type (wt) littermates (n=5) underwent [18 F]PBR06-PET/computed tomography (CT) imaging at either 9–10 months or 15–16 months of age. 7T magnetic resonance (MR) images were fused with PET/CT data (attenuation corrected) to quantify [18 F]PBR06 uptake in hippocampus (H) and cortex (Ctx). Brain sections from mice were analyzed via digital autoradiography (ARG), and subsequently stained to evaluate levels of microglia (CD68), plaques (ThioS), and TSPO. Brain [18 F]PBR06 signal was significantly higher in 15–16 month APP L/S mice compared to wts (1.36 ± 0.06 vs. 1.06 ± 0.10 %ID/g, p<0.05); however, no significant difference was found between 9–10 month old mice (p = 0.49). Analysis of specific brain regions known to contain increasing levels of microglial activation in AD revealed an even greater difference in [18 F]PBR06 signal (normalized to muscle) between 15–16 month old APP L/S and wts (Ctx: 1.52 ± 0.09 vs. 0.87 ± 0.14, p<0.005; H: 1.59 ± 0.13 vs. 0.92 ± 0.14, p<0.005). Similarly, ARG images showed significantly higher [18 F]PBR06 signal in 15–16 month APP L/S mice compared to wts (Ctx: 1.32 ± 0.04 vs. 1.00 ± 0.10 %ID/g, p<0.005; H: 1.36 ± 0.06 vs. 1.07 ± 0.01 %ID/g, p<0.05). Unexpectedly, we observed a significantly higher signal in the choroid plexus of APP L/S mice in ARG images (1.99 ± 0.05 vs. 1.53 ± 0.02, p<0.005). This is the first demonstration of TSPO-related molecular alterations in the choroid plexus of an AD mouse model. Lastly, we showed that ARG and PET results correlated well with immunostaining - i.e., increased [18 F]PBR06 uptake in brain regions containing elevated CD68, ThioS, and TSPO staining in APP L/S compared to wts. [18 F]PBR06 -PET/MR imaging shows great potential as a tool for investigating the in vivo role of microglia and TSPO in the progression and treatment of AD. Results from [18F]PBR06-PET/MRI mouse brain imaging and ex vivo autoradiography (ARG). A) Coronal PET/CT/MRI images of [18F]PBR06 accumulation in APPL/S versus wild-type (wt) mice at 15–16 months of age; B) Ex vivo ARG of coronal APPL/S and wt mouse brain sections shown on the same scale. Nissl staining of same sections are shown below for anatomical correlation. Ctx = cortex and H = hippocampus. Arrows point to choroid plexus." @default.
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• W2131433223 date "2013-07-01" @default.
• W2131433223 modified "2023-09-27" @default.
• W2131433223 title "O2-11-05: Imaging microglial activation in a mouse model of Alzheimer's disease using PET/MRI and ex vivo autoradiography" @default.
• W2131433223 doi "https://doi.org/10.1016/j.jalz.2013.04.199" @default.
• W2131433223 hasPublicationYear "2013" @default.
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