It is clear from population-level studies that there are important links between Alzheimer’s disease and obesity, altered fat metabolism, diabetes and insulin. The team demonstrated in preliminary studies that high fat diets reduced brain insulin production. Indeed, circumstantial evidence suggests that loss of brain insulin could play a role in Alzheimer’s disease, but it’s not clear if the loss of brain insulin alone is enough to cause cognitive impairment. The main goal of this project was to test the hypothesis that insulin produced in the brain is a critical factor for the survival and function of brain cells.
The team used conventional insulin 2 gene knockout mouse models to test the hypothesis that insulin plays a key role in cognition and by extension, Alzheimer’s disease. Behavioral studies with these animal models have shown impaired memory in female knockout mice. This suggests, for the first time, that insulin contributes to cognitive function, supporting the above hypothesis. Interestingly, insulin appears to have different roles in males versus females. Further behavioral studies with insulin 2 gene knockout mice are ongoing. Also, significant bioinformatic analysis of proteomic and transcriptomic data sets has been conducted to complement the group’s histological studies aimed at identifying specific brain cell types expressing insulin in human and animal models.