Microglial Activation in the Hippocampus and the Cortex in Animal Model of Alzheimer's Disease Neuropathology

Transgenic experiments have led to the development of mouse strains that express human gene mutations cloned from the DNA of persons manifesting the inherited form of Alzhiemer's Disease (AD). Double transgenic (dtg) mice were pre-treated with caloric restriction (CR) mimetic diets. One of the dtg mouse strains, Amyloid precursor protein/presenilin-1 (APP/PS1), co-expressed both the Swedish APP mutation and the ΔE9 PS1 mutation. These studies quantified the number of ionized calcium binding adaptor molecule 1 (IBA-1) positive microglial cells that resulted from neuroinflammation in the hippocampus and in the cortex. Post-fixed brain sections from the hippocampus and the cortex of dtg APP/PS1 mice and non-transgenic mice were stained with Congo red and immunostained for antibodies against IBA-1. Stereological analyses showed that the number of activated IBA-1 positive cells was positively correlated with Aβ plaque volume in the hippocampus and the cortex. This is an important finding because it indicated that one possible cause of neuropathology of AD could possibly be due to neuroinflammation that resulted from the accumulation of Aβ plaques in the brain. The model used in these investigations suggested that plaque formations could possibly have resulted from the activation of cytokines in the brain. In addition, these studies should demonstrate the effect of CR mimetic diets on the Aβ plaque deposition.