Neuropsychiatric symptoms among patients with Alzheimer's Disease: a gene-environment Interactions analysis Lead Investigator: Liming Qu Institution : University of Pennsylvania E-Mail : qul@mail.med.upenn.edu Proposal ID : 685 Proposal Description: While the apolipoprotein E gene (APOE) is recognized as a genetic risk factor for AD, ???it is neither necessary nor sufficient by itself to cause AD??? (Moceri et. al. 2001). The inability of genetic risk factors by themselves to explain the cause of AD patients raises the importance of studying the heterogeneous effect of APOE gene on the development of AD. Depression is one of the most prevalent neuropsychiatric symptoms among patients with Alzheimer???s??? disease. It is also associated with serious consequences for patients and their caregivers. Past literature has explored the possible interactive mechanism, and they found the hazard ratio of developing incident MCI given depression (vs no depression) was 2.0 but increased to 5.0 in the presence of depression and APOE gene e4 carrier status. The purpose of our analysis is to apply time series analysis into the interactive effect between the presence of depression and various AD susceptible SNPs, and we seek to analyze whether or not depression interact with recognized AD genetic risk factors to trigger the disease. In general, we will define an individual???s AD genetic risk according to his APOE allele values: high genetic risk (two e4 alleles) intermediate genetic risk (one e4 allele) and low genetic risk (no e4 alleles). Our goal is to disentangle the interactive effect of depression and genetic risk factors on AD. In order to identify the interactive effect, our analysis must include controls for clinical/medical, family, demographic, and socioeconomic characteristics of individuals. For instance, if the presence of certain co-morbidities increases the risk of AD, then failure to include these variables will overestimate the chemical effect, since it also captures the effect of co-morbidities.