Amyloid load and TSPO in APPswePS1-dE9 mice: a longitudinal study

We studied concomitantly the level of neuroinflammation and Aβ load in the APPswePS1dE9 transgenic mouse model of Alzheimer’s disease using PET imaging. The TSPO tracer [F]DPA-714 was used to measure neuroinflammation and [F]AV-45 for Aβ load in mice at 6, 9, 12, 15 and 19 months of age. At 19 months, we also analysed the neuroinflammatory and neuroanatomical status of mice brains. Imaging experiments showed that the main affected brain areas were the cortex and to a lesser extend the hippocampus, with a concomitant progression of neuroinflammation with increased amyloid burden. At 19 months, it was interesting to note that no increase in TSPO binding was observed in the cerebellum while immunostaining revealed W0-2-positive plaques. This indicated that in this region the amyloid deposits seemed not be a stimulator of inflammation. This was in agreement with the level of microglia and astrocytes staining that were observed. Our findings provide a better understanding of the relationships between neuroinflammation and plaque accumulation in the course of the disease in this mouse model. The monitoring of both processes should be of value to validate potential therapeutic approaches. Key-words: Alzheimer’s disease; Amyloid load; Neuroinflammation; PET M AN US CR IP T AC CE PT ED ACCEPTED MANUSCRIPT