Glucose Metabolism in Alzheimer’s disease: From Neuron to Brain

Alzheimer’s disease (AD) is an incapacitating condition that impairs cognition and behavior, ultimately resulting in death. It is the 6th leading cause of death in the United States:  it affects more than 5 million Americans, but a disease modifying treatment does not exist. AD is characterized by progressive neurodegeneration associated with amyloid plaque formation and tangle deposition in the cortex and hippocampus of the brain Reilly 2003. Although AD has been intensively studied in recent decades, the causes and the exact molecular pathology that triggers the disease in most patients remains unknown. Specifically, only 5% of patients with early onset AD possess genetic mutations associated with the disease REILLY 2005. Interestingly, there is an epidemiological association between diabetes, high blood glucose levels and AD but a molecular mechanism linking high glucose levels and the induction of the molecular changes associated with Alzheimer’s disease has not been studied. We created a multidisciplinary team at Temple University to investigate the association between pathological glucose metabolism and neurodegeneration. We will apply state of the art metabolomics, proteomics and drug screening platforms to determine the effect of high glucose levels on primary neuronal cells and animal brains. The ultimate goal of our project is to achieve a better understanding of the molecular mechanisms involved in the early stages of AD. Knowing these mechanisms will allow us to identify novel therapeutic targets and generate invaluable tools for the development of effective therapies against Alzheimer’s disease.

Project Description