Gerontological Nursing Interventions Research Center (GNIRC)

Title: African American AD Genotype-Phenotype Profiles
Principal Investigator : Debra Schutte, PhD, RN
Study Site : University of Iowa

Abstract
Alzheimer disease (AD) is a prevalent age-modulated neurodegenerative disorder. The clinical phenotype in AD is characterized by progressive deterioration in cognitive ability that impacts functional and social performance. Yet significant individual variability exists in the rate, patterns, and domains of impairment experienced among persons with AD. A growing number of genetic variants are known to contribute to the risk for developing AD. There also is evidence that the disease risk associated with genetic variants differs across ethnic groups. However, the single or collective contribution of candidate susceptibility genes to the variability in disease course among persons with AD remains largely unknown, both within a single population and across diverse ethnic populations. This knowledge gap prevents healthcare providers from identifying clinical subgroups of AD based upon genotype that may differentially respond to biobehavioral interventions. This application proposes a pilot observational epidemiologic study to explore the relationships between genetic variants and phenotypic variability among persons with AD in an African American population. The specific aims of the study are to: 1) establish the feasibility of the recruitment protocols, data collection protocols, and instrument performance needed to conduct a genotype-phenotype correlation study within an African American population of persons with AD, 2) identify candidate susceptibility genes that modify disease trajectory, cognition, function, and behavior within an African American population of persons with AD, and 3) compare and contrast AD phenotypic variability and modifier gene profiles between this African American sample and an existing comparable dataset from a Caucasian population. Persons with probable AD will be recruited from a long-term care facility. DNA will be isolated from cheek swabs and genotyped for known variants within several candidate genes. Subjects with AD also will complete a phenotype battery consisting of measures of cognition, function, and behavior at baseline and a 4-month interval. Data generated from this pilot will provide direction for subsequent grant applications for external funding to support a large, prospective, cross-ethnic genotype-phenotype correlation study in persons with AD. Ultimately this research will guide the development and testing of genotype-directed biobehavioral interventions for persons with AD based upon an empiric understanding of the full AD trajectory across diverse populations.