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Differential Effects of Diet- and Genetically-Induced Brain Insulin Resistance on Amyloid Pathology in a Mouse Model of Alzheimer’s Disease

Diabetes is a known risk factor for age-related diseases of the eye and brain (see Glaucoma and Diabetes and Diabetes: A Modifiable Risk Factor for Alzheimer's Disease). The biological explanation for the association of these diseases is not settled science. Researchers in Japan have recently concluded that amyloid plaques, a hallmark of Alzheimer’s disease, result from insulin resistance that was reversed with an improved diet. 

We recognize that results from mice grown for research that have been genetically modified and fed a specifically synthesized food cannot be applied to human beings without a strong dose of healthy skepticism on the side. However, the coincidence of type 2 diabetes and Alzheimer’s is well established among medical experts. By using mouse models, Dr Takeshigroup at The University of Tokyo were able to manipulate diet-induced obesity and insulin resistance at specific stages of the brain developing amyloid beta plaques. Mice do not, without manipulation by scientists, develop these plaques. A diet that was high in fat developed insulin resistance and two times more amyloid beta plaques. 

By studying the brains of these mice, the scientists found that the APP protein that is broken up into amyloid beta is not different in the diabetic animals. In their experiments, it was determined that the plaques of animals with high fat diets resisted break up by various biochemical processes. 

If animals had their diet changed before the amyloid plaques developed (but after the amyloid has started to be produced), lost weight and resolved the insulin resistance, then their brains were comparable to the animals fed a regular diet. 

These results demonstrated that controlling diet can reverse the deteriorating effect of HFD on brain amyloid pathology even after HFD-induced elevation of Aβ levels has been initiated.

In a growing body of scientific research on the connection between diet-induced obesity, it is encouraging to see results on the positive impact on diet on Alzheimer’s outcomes. 

Learn more about Molecular Neurodegeneration, the official journal of BrightFocus.

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