Project Overview

One percent of Alzheimer’s disease is the early-onset type that runs in families. Extensive studies of these ultra-rare forms of Alzheimer’s disease have revealed the genes that cause them. On the other hand, the most common forms of Alzheimer’s disease are surprisingly understudied and poorly understood at the level required for therapeutic intervention. However, it is clear from population levels studies that there are important links between Alzheimer’s disease and obesity, altered fat metabolism, diabetes and insulin. Interestingly, there have been many reports over the years that the brain actually produces a small amount of insulin. James Johnson and his team recently validated these findings using rigorous controls and found in preliminary studies that high fat diets reduced brain insulin production. In this project, the team is testing the hypothesis that insulin produced in the brain is a critical factor for the survival and function of brain cells in the context of both a genetic change that increases Alzheimer’s risk and a diet that increases Alzheimer’s risk. They will employ new strains of mice engineered to lack insulin, only in the brain that were not available until recently. Previous studies employed crude toxins to kill the insulin producing cells in the brain and were therefore not definitive. The team will examine the survival and function of the brain cells in these mice that lack brain insulin. They will also assess their ability to learn and study how their brains are reprogrammed in the absence of insulin. Insulin will be correlated with Alzheimer’s-like changes in human brains. These studies are likely to impact our understanding of Alzheimer’s disease, potentially revealing a path to a cure.