2012 Grants - Casadesus Smith

Modulation of Metabolic Processes to Prevent Alzheimer's Disease

Gemma Casadesus Smith, Ph.D.
Case Western Reserve University
Cleveland, Ohio

2012 Investigator-Initiated Research Grant

Metabolic conditions and diseases—such as obesity, insulin resistance and diabetes—have been shown to be associated with increased risk of Alzheimer's disease. One hormone that regulates metabolism is leptin; low leptin levels have also been associated with increased risk of Alzheimer's disease and reduced cognitive function in older people. Furthermore, some mice that have Alzheimer's-like brain degeneration show improved cognitive function with leptin treatment.

Gemma Casadesus Smith, Ph.D., and colleagues have obtained evidence that low levels of another hormone, amylin, are also associated with increased risk of Alzheimer's disease and reduced cognitive function. From biochemical studies, it is known that leptin and amylin work together and may enhance each other's effects on metabolism.

Dr. Casadesus Smith and colleagues have proposed to study whether combination treatments of leptin plus amylin can improve cognitive function more than either hormone acting alone. They will conduct these experiments in mice that have been genetically engineered to have Alzheimer's-like brain degeneration. The researchers will compare the effects of each hormone alone with the effects of the two together. In addition to measuring cognitive function, they will study brain structure and how it is affected by each treatment. These studies will examine the effects of hormones that have the potential to be developed into treatments to prevent or slow the progression of Alzheimer's disease in humans.