P3-032: Validation of an association between the CETP I405V variant and cognitive decline: The Cache County Study

Alzheimer's is a fatal, non-treatable neurodegenerative disease and the most common cause of dementia. While no one gene has been found to determine the development of Alzheimer's, past studies have established a strong hereditary influence on Alzheimer's. So far, only 5 genes have been found which replicably contribute to the genetic risk of developing Alzheimer's. However, the gene for Chlolesteryl Ester Transfer Protein (CETP) has been identified as a possible new contributor to the genetic risk factor. In order to test this association we obtained data on over 4000 subjects studied in the Cache County Study on Memory, Health and Aging over a 15-year period. This data included DNA samples, cognitive decline rates and incidence of dementia–particularly Alzheimer's Disease. DNA samples were genotyped for rs5882 using quantitative PCR. The SNP genotypes and corresponding phenotypes for each subject were then analyzed for association using mixed linear models and for survival, or the amount of time until the disease appeared, using Cox proportional hazard models. Our results showed that each valine allele lowers baseline score on the Modified Mini Mental State Examination by an average of 4.1 points. Each additional valine also decreases the rate of decline by 0.6 points/year on average. I405V homozygosity is associated with a lower baseline cognitive ability but a slower cognitive decline. We did not find any significant association between this SNP and risk of Alzheimer's disease.