Assessing Alzheimer\u27s disease phenotypes in a type 2 diabetic mouse model.

Increasing evidence suggests a link between type 2 diabetes (T2D) and Alzheimer\u27s disease (AD), yet limited studies have been performed to elucidate this relationship. The Howell lab has created a new mouse model by introducing two early-onset AD mutations (APpswe and PS1de9) into the New Zealand Obese (NZO) mouse strain that develops T2D. We characterized the NZO.APPIPS1 model for hallmark features of AD to assess whether specific features of AD are exacerbated by diabetes. In particular, we tested the hypothesis that diabetes would induce neuroinflammatory responses. Brains from 8-month-old mice were harvested, sectioned, and assessed for microglial and astrocytic reactivity. Silver staining and ThioS staining were also used to visualize plaque morphology. Western blotting was utilized to quantify tau protein, and ELISA was used to quantify amyloid beta 42 (A~42) levels. Although there were fewer plaques in the NZO.APPIPS1 mice compared to B6.APPIPS1 mice, the plaques were larger. However, there was no significant difference in A~42 levels, implicating that plaque clearance mechanisms were affected in NZO.APPIPS1 mice. Diabetes may impact plaque morphology as microglia were observed around blood vessels in the NZO WT mice. This suggests that diabetes may lead to vascular damage and thus, impaired plaque clearance through the blood vessels. This could explain the observed larger plaque size in NZO.APPIPS1 mice.