Presenilin1 Function and its Role in Alzheimer's Disease

Alzheimer’s disease (AD) is one of the most common causes of death. It is estimated that more than four million people are affected by this disease and this number is expected to double during the next forty years as the population ages. Some of the genetic defects, i.e., mutations in our genetic materials (genes) that cause AD have been identified. Most recently, a gene named presenilin-1 (PS-1), has been found to be closely associated with AD. Many missense mutations have now been reported in the PS-1 gene and these mutations account for a significant fraction of AD patients. However, functions of PS-1 gene product and mechanisms by which mutations in this gene cause AD are not known. To study functions of the PS-1 gene and understand its role in pathogenesis of AD, we propose to identify interaction partners of the PS-1 gene product using both genetic and biochemical assays which we have previously successfully used for studying other genes. Examining the interaction partners of PS-1 gene product will provide insight into biological function of the PS-1 gene and will further our understanding how the mutations in PS-1 gene lead to development of AD. In addition, this study may also reveal other new genes involved in pathogenesis of AD. With a pilot project grant from National Institute of Aging through Alzheimer’s Disease Research Center of Washington University, we have made significant progress on the project proposed and obtained some exciting preliminary results. Further support from American Health Assistance Foundation will be essential for continuation and further expansion of this project.