Study of a Novel Genetic Risk Factor for Alzheimer's Disease

This study aims to determine the extent to which a novel genetic risk factor for Alzheimer’s disease drives changes in gene and protein expression in brains of mice like the ones observed in human Alzheimer’s brains.

Dr. Tesco’s lab recently found a novel genetic variant associated with late-onset Alzheimer’s disease in African American families, called GGA3. Her research previously demonstrated that GGA3 plays a critical role in the transport and regulation of BACE1, a key enzyme responsible for amyloid-beta production. The study aims to determine how this novel genetic variant leads to Alzheimer’s disease. Results may contribute to a better understanding of genetic risk factors in the African American population, which is currently understudied.

GGA3Ins545T is a rare variant that co-segregate with AD in African American (AFR) subjects. Although the risk of AD in AFR is twice as high as in Caucasian population, there are very few population-based genetic association studies. Thus, our studies may contribute to a better understanding of genetic risk factors in the AFR population, which are currently understudied.

The multi-disciplinary phenotyping of a novel mouse model carrying a genetic variant associated with LOAD in the AFR population is expected to identify the relevant pathways leading from GGA3 malfunction to AD phenotypes and identify drug-targetable genes that may improve outcomes in AD patients carrying this mutation.