Alzheimer’s disease (AD) is the sixth leading cause of death in the US. Some
researchers refer to AD as “Type III Diabetes” because of reported glucose metabolism
dysfunction. Preclinical studies suggest increasing insulin decreases AD pathology, although
the mechanism remains unclear. To sensitize insulin signaling, this study activated
Peroxisome Proliferator-Activated Receptor Gamma using intranasal co-administration of
pioglitazone (PGZ) and insulin. This method targeted the site of action to reduce peripheral
effects and to maximize impact in transgenic mice expressing AD pathology. Data from
GC-MS fluxomics analysis suggested that PGZ+Insulin increased glucose metabolism in the
brain. Immunohistochemistry with relevant antibodies was used to identify AD pathological
markers in the subiculum, indicating that PGZ+Insulin decreased pathology compared to
Insulin and Saline. This suggests that increasing glucose uptake in the brain alleviated AD
pathology, further clarifying the role of insulin signaling in AD pathology.Gemston