Alzheimer’s disease is the leading cause of dementia and the sixth leading cause of death in the U.S. The disease has both genetic and environmental risk factors, and up to a third of cases may be the result of modifiable lifestyle influences such as a diet high in saturated fat and sugar.
Individual genetic variation affects how environmental risk factors may raise or lower a person’s risk for Alzheimer’s disease, but these gene-by-environment interactions are poorly understood.
The Alzheimer’s Association has awarded a three-year research fellowship totaling $174,973 to Amy Dunn, Ph.D.Gene-environment interactions in aging, Alzheimer's disease, and related disordersAmy Dunn, Ph.D. , a postdoctoral associate in the laboratory of Jackson Laboratory (JAX) Associate Professor The Kaczorowski LabI lead a collaborative and interinstitutional research program that uses a multidisciplinary approach to identify early causative events underlying ‘normal’ nonpathological age-related memory decline and Alzheimer’s dementia.Catherine Kaczorowski, Ph.D. , for her studies of how genetics and diet interact to determine risk for Alzheimer’s disease.
Gene-by-environment interactions are difficult to study in humans, Dunn notes, because clinical studies are inconsistent in their reporting of modifiable risk factors such as diet. Traditional mouse models of Alzheimer’s disease have no genetic variation, and therefore are also poorly suited for understanding the effects of diet on a genetically varied population.
“To overcome these barriers,” Dunn explains, “we developed a mouse model of Alzheimer’s disease with a portion of the genetic variability observed in humans, allowing us to study complex genetic and environmental contributors to the disease.”
How do you make a Western diet — for a mouse?Researchers at JAX are exploring the role of diet in a myriad of diseases related to aging, including glaucoma and Alzheimer's disease.Dunn will feed the mice a diet high in both fat and sugar. “I will then measure memory function, analyze gene expression and identify novel genes and gene networks that mediate the effects of a high-fat, high-sugar diet on memory function.”
These studies, she says, “have the potential to identify new therapeutic targets for Alzheimer’s disease, in addition to enhancing our ability to develop personalized treatment strategies based on a person’s genetic and environmental risk factor profile.”