A number of studies have found that African Americans have significantly higher prevalence and incidence of non-familial Alzheimer's Disease (AD) than Caucasians. However, because the cognitive tests used in part to diagnose AD have low specificity among African Americans, it is unclear whether misdiagnosis contributed to these findings. If rates of AD are in fact elevated, these studies suggest that different genetic or environmental factors may influence AD risk among African Americans. While the APOE D4 allele, the major genetic risk factor for AD, is more frequent among African Americans, the relative risk is somewhat lower than in other populations. It is possible that the association of APOE with AD is modified by the presence and severity of cardiovascular and cerebrovascular disease. The current proposal will address these issues by conducting a genetic association study of AD among African Americans with a carefully refined phenotype, including cognitive test performance, cardiovascular health, and brain imaging data. We propose a collaborative study to be conducted at four sites which specialize in assessment of AD and serve large populations of African Americans: Columbia University in New York City, Duke University and North Carolina A&T State University in North Carolina, and Vanderbilt University in Tennessee. We will 1) refine the phenotype of AD among African Americans by incorporating our past work on the role of cultural and educational experience on cognitive test performance in order to provide accurate diagnoses of AD, collect biomarkers related to subclinical cardiovascular disease, and obtain MRI brain images to quantify volume of white matter hyperintensities, infarct burden, and total brain; 2) we will test the association of select candidate genes in matched African American AD cases and controls, and examine the effect of cardiovascular and cerebrovascular disease as potential modifiers of risk; and 3) we will examine genotype- phenotype relations among candidate genes and several quantitative traits, including performance on measures of learning and memory, age at onset of AD, and cardiovascular and cerebrovascular disease burden. ? ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG028786-02S1
Application #
7643644
Study Section
Special Emphasis Panel (ZRG1-HOP-B (02))
Program Officer
Anderson, Dallas
Project Start
2007-09-15
Project End
2012-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
2
Fiscal Year
2008
Total Cost
$25,000
Indirect Cost
Name
Columbia University (N.Y.)
Department
Neurology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Cukier, H N; Kunkle, B K; Hamilton, K L et al. (2017) Exome Sequencing of Extended Families with Alzheimer's Disease Identifies Novel Genes Implicated in Cell Immunity and Neuronal Function. J Alzheimers Dis Parkinsonism 7:
Mez, Jesse; Chung, Jaeyoon; Jun, Gyungah et al. (2017) Two novel loci, COBL and SLC10A2, for Alzheimer's disease in African Americans. Alzheimers Dement 13:119-129
Kunkle, Brian W; Jaworski, James; Barral, Sandra et al. (2016) Genome-wide linkage analyses of non-Hispanic white families identify novel loci for familial late-onset Alzheimer's disease. Alzheimers Dement 12:2-10
Hohman, Timothy J; Cooke-Bailey, Jessica N; Reitz, Christiane et al. (2016) Global and local ancestry in African-Americans: Implications for Alzheimer's disease risk. Alzheimers Dement 12:233-43
Ghani, Mahdi; Reitz, Christiane; Cheng, Rong et al. (2015) Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals. JAMA Neurol 72:1313-23
Gross, Alden L; Benitez, Andreana; Shih, Regina et al. (2015) Predictors of Retest Effects in a Longitudinal Study of Cognitive Aging in a Diverse Community-Based Sample. J Int Neuropsychol Soc 21:506-18
Sisco, Shannon; Gross, Alden L; Shih, Regina A et al. (2015) The role of early-life educational quality and literacy in explaining racial disparities in cognition in late life. J Gerontol B Psychol Sci Soc Sci 70:557-67
Schneider, Brooke C; Gross, Alden L; Bangen, Katherine J et al. (2015) Association of vascular risk factors with cognition in a multiethnic sample. J Gerontol B Psychol Sci Soc Sci 70:532-44
Hamilton, Jamie L; Brickman, Adam M; Lang, Rosalyn et al. (2014) Relationship between depressive symptoms and cognition in older, non-demented African Americans. J Int Neuropsychol Soc 20:756-63
Zahodne, Laura B; Nowinski, Cindy J; Gershon, Richard C et al. (2014) Depressive symptoms are more strongly related to executive functioning and episodic memory among African American compared with non-Hispanic White older adults. Arch Clin Neuropsychol 29:663-9

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