Project Summary Alzheimer's disease (AD) affects 5.8 million people in the United States and is an immense burden on our economy, patients and caregivers. Genome-wide association studies (GWAS) have successfully led to 25 genome-wide significant loci associated with AD risk and many more associations with key clinical covariates. Most of these findings are made on participants with European ancestry, although efforts to study other minority populations are taking off. Knowledge about AD genetics among Asian Americans is especially limited due to lack of participants. Comprising 6% of the US populace, Asian Americans are under-sampled and deserve more scientific investment. We propose the Asian Cohort for Alzheimer's Disease (ACAD), the first large Alzheimer's Disease (AD) genetics cohort for Asians in United States (US) and Canada. To optimize ACAD's success, we assembled a team of scientists, clinicians, and community partners with collaborative history and expertise in AD research, human genetics, and Asian community outreach. We propose to recruit 5,970 participants aged 60 years or older and of Chinese, Korean, and Vietnamese ancestry from metropolitan areas across the US and Canada in collaboration with community partners, clinics, or nursing homes that serve Asian communities. We will collect saliva for DNA and use validated, localized instruments, data forms, and clinical/diagnostic protocols. To support these recruitment and data collection activities, we will set up a coordinating center and develop governance, community outreach and training programs to support recruitment and analysis activities, and conduct a process evaluation of the recruitment and outreach efforts. All samples will be genotyped using SNP arrays and imputed using a large Asian-specific reference panel of whole genome sequencing data from international Asian cohorts. We will analyze genetic and clinical data to investigate impact of lifestyle risk factors, genetic variants for AD risk, evaluate differential effects of sex and APOE genotypes on AD risk, and predict clinical diagnosis of AD using genetic and lifestyle risk scores. We will replicate these findings through meta-analysis collaborations with international Asian cohorts and AD studies from other populations. Comprising 6% of the US populace, Asian Americans are under-sampled and deserve more scientific investment in Alzheimer's disease research. The ACAD project will build the first major AD genetics study for Asians in the US and Canada. Successful completion will lead to new genetic and lifestyle screening markers for Asian Americans and insights about novel therapeutic targets for AD. ACAD will be a first network for recruiting and studying AD in Asian Americans that will extend to Asian Indians, Filipino and other Asian American populations in the future, serving the unmet needs of Alzheimer's disease research for Asian Americans.