Grant: Institute of Genetics Clinical Investigatorship Award

The cause of Alzheimer Disease and other related dementias is complex, and likely involves both inherited and environmental factors. With advances in high throughput molecular genetic techniques, it is now possible to carry out genomewide association studies, which is a powerful method to identify the genetic differences in each person to determine the contribution of inherited factors in the development of diseases. However, the cost of performing such analysis is still very expensive. One way to reduce the cost is to use pooled DNA from the whole collection of samples for analysis. In this project, we will utilize the highly characterized clinical samples from the UBC-Clinic for Alzheimer Disease and Related Dementias and the Canadian Cohort Study of Cognitive Impairment and Related Dementias to examine the interplay of genetic and environmental factors in the development of Alzheimer Disease and other related dementias using a 2-step analysis. Firstly, we will perform a genomewide association study using pooled-DNA analysis from the two cohorts. Secondly, we will select from the results candidate genes for further analysis to examine the role of these genes and their potential interactions with clinical and epidemiological factors that confer risks to developing Alzheimer Diseases and other dementias. We have collected detailed longitudinal data in our subjects that will allow us to examine these effects. The role of this project is two-fold. Identification of novel genetic factors will improve our understanding of the pathogenesis of neurodegenerative dementias and expedite development of new therapy for treatment of these diseases. Success with this approach will also provide empirical evidence that such this paradigm can be used for analysis of other complex genetic traits.