ABSTRACT Mendelian mutations, common risk factors, and ? more recently ? rare risk-associated variants have been identified in neurodegenerative dementia. Yet, a significant proportion of the heritability for Alzheimer's Disease (AD) and Frontotemporal Dementia (FTD) remains unexplained, strongly suggesting that additional genetic risk factors await to be identified. Over the past 9 years, the Genetics Core has supported PPG investigators by 1) collecting and storing DNA and RNA samples from the entire PPG cohort; 2) providing genetic testing for known pathogenic causes of dementia and risk-associated variants; 3) contributing to the discovery of novel genes and novel risk-associated variants; 4) establishing an informatics platform to facilitate data sharing, storage and mining. In this renewal application, we propose to efficiently leverage this infrastructure and expertise, so as to expand the portfolio of genetic and genomics assays available to PPG investigators. We propose to continue sample collection and banking, to expand our sequencing and genotyping efforts to include all the known causes of Mendelian forms of dementia, the top disease susceptibility variants, and genome sequencing in a subset of the PPG cohort. These studies will contribute to a better patient characterization, and pave the way for subject selection and stratification based on genetic profiling in future clinical trials. Given the fundamental nature of genetic information in etiology and pathophysiology of FTD, this Core serves all of the projects in this program and is linked to the other PPG cores.