Current Research: Alzheimer's Disease
Tau protein phosphorylation is increased in diabetic mouse brains compared to control.Alzheimer’s disease (AD) is the major cause of dementia in the United States. AD is characterized by progressive memory loss, impaired language, and behavioral changes. In 2000, an estimated 4.5 million people had AD and this number will grow to over 13 million by 2050. According to estimates used by the Alzheimer’s Association and the National Institute on Aging, national direct and indirect annual costs of caring for individuals with AD are at least $100 billion. The average lifetime cost of care for an individual with AD is $174,000 (www.alz.org).
Diabetes mellitus affects over 20 million people in the United States. The number of diabetes patients is increasing by 5 percent per year and one in three Americans born in 2000 will likely develop diabetes in their lifetime. The annual cost of diabetes in medical expenditures and lost productivity climbed from $98 billion in 1997 to $132 billion in 2002 and the direct medical costs of diabetes more than doubled in that time, from $44 billion in 1997 to $91.8 billion in 2002 (www.diabetes.org). While no accurate figures are yet available, the projected annual cost of diabetes in 2006 is more than $150 billion.
People with diabetes have an increased risk of developing AD compared to age and gender matched patients without diabetes. Type 2 diabetes have greater than a two-fold increased risk of developing AD compared to individuals without type 2 diabetes. High glucose level in diabetic patients is associated with impaired cognitive performance tests and an increased number of mental subtraction errors in individuals with types 1 and 2 diabetes. A recent study of the Mayo Clinic AD Patient Registry reveals that 80 percent of AD patients have either type 2 diabetes or impaired fasting glucose level. Many features of the metabolic syndrome, including obesity, dyslipidemia and high blood pressure are risk factors not only for diabetes and cardiovascular disease, but also AD. This link has led researchers to search for the mechanism underlying diabetes-related AD progression.
PNR&D researchers are investigating the possible link between AD and diabetes using cellular and animal models. Two of the most prominent pathological characteristics of AD are the accumulation of b-amyloid in extracellular plaques and the appearance of intracellular neurofibrillary tangles. We found that tau, the major component of the tangles, is abnormally regulated in hyperglycemic conditions both in vitro cell culture systems and in vivo diabetic animals. We are trying to develop new animal models to study the mechanisms underlying the interaction of these two highly 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 AD.
