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  • Create Date June 22, 2018
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Effects of hyperglycemia in the APP/PS1 mouse model of Alzheimer's disease

Alzheimer’s disease (AD) is a debilitating neurodegenerative disorder that is characterized by memory deficits, neuronal loss, and death. Pathological hallmarks of the disorder include the accumulation of amyloid beta (Ab) plaques and neurofibrillary tangles composed of hyperphosphorylated tau (ptau). An additional characteristic of AD includes a sustained inflammatory response (neuroinflammation) within the brain that has been demonstrated to promote and accelerate AB and ptau pathology. The cause of AD remains unknown but a number of risk factors exist for sporadic AD (sAD) that accounts for 95%-98% of all AD cases.

     Risk factors for sAD include cardiovascular disease, obesity, and diabetes mellitus (DM). DM in particular is of interest as it induces hyperglycemia and insulin receptor resistance that impact the vasculature and inflammation. What remains to be elucidated is the exact mechanisms in DM that confers greater risk for developing AD, or exacerbates AD pathology. We evaluated the effects of hyperglycemia in the APP/PS1 mouse model of AD versus wild-type (wt) controls. We have previously demonstrated that staggered administration of streptozotocin (stz) induces a sustained hyperglycemic state that results in several AD pathologies, including neuroinflammation. In the present study we evaluated if the same hyperglycemia exacerbated AD related  pathology in the APP/PS1 mouse model of AD. We performed these investigations in male and female mice to determine if differences exist based on sex. Our data indicate that several measures of AD were altered by the combination of APP/PS1 and stz. This includes differences in male vs. female mice.

This project was funded by NIGMS P20 COBRE award P20GM109025 as part of the Center for Neurodegeneration and Translational Neuroscience (CNTN).