Microglial activation in the right amygdala-entorhinal-hippocampal complex is associated with preserved spatial learning in App mice

In Alzheimer`s disease (AD), regional heterogeneity of ?-amyloid burden and microglial activation individual patients is a well-known phenomenon. Recently, we described high incidence inter-individual in terms asymmetry plaque mouse models AD as assessed by positron-emission-tomography (PET). We now investigate the associations between amyloid burden, activation, impaired spatial learning performance transgenic mice vivo. 30 AppNL-G-F (15 female, 15 male) acquired cross-sectional 18 kDa translocator protein (TSPO-PET, 18F-GE-180) ?-amyloid-PET (18F-florbetaben) scans at ten months age. Control data were obtained from age- sex-matched C57BI/6 wild-type mice. (i.e. Morris water maze) within two weeks PET scanning correlated principal component scores with voxel-wise TSPO tracer uptake maps mice, controlled for age sex. order to assess effects hemispheric asymmetry, also analyzed correlations bilateral regions interest frontal cortex, entorhinal/piriform amygdala, hippocampus, using regression model. tested correlation biomarkers performance. Voxel-wise analyses revealed that higher TSPO-PET signal entorhinal piriform cortices, hippocampus hypothalamus Region-based analysis showed significant expression right cortex amygdala performance, whereas there no such left hemisphere. Right lateralized predicted better maze (? = -0.470, p 0.013), irrespective global level. results amyloid-PET learning. Elevated amygdala-entorhinal-hippocampal complex associated Our findings support protective role microglia on cognitive function when they highly express specific brain involved memory.