Alzheimer’s Disease

Tau protein phosphorylation

Tau protein phosphorylation is increased in diabetic mouse brains compared to control.

Recently it has become apparent to health scientists that people with diabetes have an increased risk of developing Alzheimer’s disease compared to people without diabetes. PNR&D scientists are interested in understanding the link between diabetes and Alzheimer’s disease so that treatment approaches can be developed to prevent or improve Alzheimer’s disease onset and progression in diabetic patients.

Why patients with diabetes are more likely to develop Alzheimer’s disease

The underlying biological mechanisms that link the development of diabetes with Alzheimer’s disease are not fully understood. Certain features, however, that are common to both disorders could provide insight into the contributing mechanisms. These features include, but are not limited to, abnormal protein processing, impaired insulin signaling, dysregulated glucose metabolism, oxidative stress, the formation of advanced glycation end products, and the activation of inflammatory pathways.

Current research in the PNR&D is focused on investigating the mechanisms that link diabetes and Alzheimer’s disease using both cellular and animal models. Two of the most prominent pathological characteristics of Alzheimer’s disease are the accumulation of β-amyloid in extracellular plaques and the appearance of intracellular neurofibrillary tangles. Results indicate that tau, one of the major components of the tangles, is abnormally regulated during hyperglycemic conditions in cell culture systems and in diabetic animals. Therefore, PNR&D investigators are trying to develop new animal models to study the mechanisms underlying the interaction of these two pandemic diseases. Successful completion of our studies will give a fundamental basis for drug development and lifestyle modifications aimed at treating and/or preventing diabetes and Alzheimer’s disease.

How insulin resistance affects Alzheimer’s disease progression

Obesity is one of the greatest risk factors for diabetes and currently, nearly one-third of adults in the United States are obese. Obesity is accompanied by impaired fat metabolism and impaired insulin signaling or resistance. This insulin resistance occurs in various tissues, including neurons. Impaired insulin signaling is also associated with cognitive impairment and Alzheimer’s disease. In fact, impaired insulin signaling impacts the expression and metabolism of the proteins β-amyloid and tau, which become hallmark components of the brain pathology that characterizes Alzheimer’s disease.

Scientists in the PNR&D are working to understand how obesity-related insulin resistance in neurons impacts cognitive impairment and Alzheimer’s disease pathology like β-amyloid extracellular plaques and intracellular neurofibrillary tangles containing tau. A better understanding of this relationship will aid in the development of much-needed therapies to treat and prevent Alzheimer’s disease onset and progression in obese or diabetic individuals.

Stem cells in the treatment of Alzheimer’s disease

Scientists in the PNR&D have demonstrated that stem cell therapies improve outcomes in models of amyotrophic lateral sclerosis (ALS) and is now conducting an FDA-approved clinical trial in ALS patients. Now, the PNR&D is working to develop a similar breakthrough treatment for Alzheimer’s disease (AD). Preliminary studies in a model of early-onset AD show that delivery of our unique line of human neural stem cells directly to the brain improves memory and learning deficits and reduces the buildup of amyloid plaques. We are now performing comprehensive testing in additional models that display many characteristics found in human AD, to determine exactly how these stem cells impact disease processes and cognition.