Advertisement

AMYLOID-INDUCED MICROGLIAL ACTIVITY IN THALAMOCORTICAL CIRCUITS PREDICTS SUBSEQUENT COGNITIVE DECLINE

      Background

      Although the signature properties of Alzheimer’s disease (AD), such as the formation of amyloid plaques, activation of inflammatory responses, and hyperphosphorylation have been well studied, the explanation illustrating a clear relationship specifically between neuroinflammation and cognitive impairment has not yet been discovered. Thus in this article, we employed the McGill-R-Thy1-APP transgenic (Tg) rat model to observe for activation of inflammatory responses and the presence of cognitive decline. We hypothesize that early expression of neuroinflammatory signals will lead to future cognitive decline in the amyloid expressing animals.

      Methods

      Microglial activation was measured using the ligand [18F]PBR06 for PET, while cognitive performance was measured with the MWM task in 5 wild-type (Wt) and 8 Tg rats at baseline (BL; 11.5 months) and at follow-up (FU; 16 months). PBR-PET images were processed using the cerebellar grey matter as the reference region and cognitive measurement was calculated as the average times of day 3 and 4 of the water maze task. The baseline as well as the change (FU – BL) in the cognitive measurements were correlated at voxel level using “VoxelStats” toolbox to observe for the effect of group and PBR interaction on the change in the water maze performance. The PBR values were corrected for global cortical values, and t-statistical maps were generated to illustrate the regions of significance.

      Results

      The association between baseline levels of cognition and inflammation was greater in the Tg than Wt rats in the right nucleus accumbens, whereas in the opposite was seen in the right inferior colliculus. The association between baseline levels of inflammation and change in cognition at follow-up, several regions including the left retrosplenial cortex, right hippocampus, and the right posterior commissure showed higher decrease in cognition of the Tg animals compared to the Wt (Figure 1).

      Conclusions

      At baseline, there is no association between neuroinflammation and cognitive performance; however in more aged rats, baseline levels of PBR is able to predict cognitive decline. The results provide a framework that could potentially be applied in human studies focusing on the detrimental roles of neuroinflammation in AD.
      Figure thumbnail fx1