Linking Diabetes to Alzheimer's Disease in Neuroblastoma Cells via TGFbeta1

Alzheimer's Disease (AD), the leading cause of dementia in elderly people, is frequently associated with cerebral amyloid beta (Abeta) plaques, and an increased ratio of Abeta42/Abeta40 isomers has been connected to an increased prevalence of these plaques. Type 2 diabetes mellitus (T2D), a failure to properly respond to insulin, has been noted to increase the risk of AD; although this connection is not yet fully understood, TGFbeta1, a cytokine that regulates a variety of cellular functions, is suspected to be heavily involved. The purpose of this experiment is to identify the role of TGFbeta1 in increasing the Abeta42/Abeta40 ratio in BE2-M17 neuroblastoma cells under T2D conditions. It was hypothesized that if under T2D conditions, the BE2-M17 cells would yield an increased Abeta42/Abeta40 ratio and TGFbeta1 levels. Additionally, it was hypothesized that they would yield a normal Abeta42/Abeta40 ratio even under T2D conditions if the TGFbeta1 signaling pathway were inhibited. The ELISA results for Abeta40 and 42 levels report that individually, glucose and insulin exposure have no significant effect on Abeta40 levels, but simultaneously decreased glucose, insulin, and insulin-like growth factor 1 exposure significantly increase Abeta42 levels. This suggests that a combination of hypoglycemia and hypoinsulinemia increases the risk of AD.