application): Alzheimer's disease (AD) is the most common cause of dementia in the elderly. In the U.S., approximately 3-4 million persons are affected by this disease, costing the U.S. economy more than $50 billion per year. The cause(s) of this debilitating neurodegenerative disease is (are) presently unknown. However, a large body of evidence indicates that at least some, if not all, AD cases are due to genetic factors. Genetic analysis of families with multiple cases of early-onset AD has shown that three autosomal dominant genes are responsible for at least some occurrences of the disease. In these families, offspring of affected persons are at 50% risk of inheriting a familial AD (FAD) gene and developing AD. Late-onset FAD (LOFAD) seems to involve other genes and is a more complex disease. Using linkage analysis and other sophisticated statistical genetic methods, the long-range goal of this project is to identify the underlying causes of AD by identifying the genes responsible for the genetic forms of this disease. Four genetic loci have been identified which are heritable factors in AD: the amyloid precursor protein (APP) gene, presenilin 1 (PS 1 )on chromosome 14, presenilin 2 (PS2) on chromosome 1, and a susceptibility locus at the ApoE gene/region on chromosome 19. The following Specific Aims of this project address characterizing existing AD genes and mapping new AD loci: 1) Identify and sample new FAD kindreds. 2) Identify the chromosomal regions containing LOFAD loci. 3) Identify chromosomal regions containing genes that modify age of onset of AD in Volga German families with a specific PS2 mutation. 4) Characterize the relationship between ApoE genotypes and FAD in the presence of other covariates. Identification of FAD genes and modifying factors will facilitate establishing the etiology of AD, lead to better diagnostic methods, and potentially provide a rationale for designing therapeutic and preventive measures.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Specialized Center (P50)
Project #
5P50AG005136-19
Application #
6593353
Study Section
Project Start
2002-06-01
Project End
2003-04-30
Budget Start
Budget End
Support Year
19
Fiscal Year
2002
Total Cost
Indirect Cost
Name
University of Washington
Department
Type
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Young, Jessica E; Fong, Lauren K; Frankowski, Harald et al. (2018) Stabilizing the Retromer Complex in a Human Stem Cell Model of Alzheimer's Disease Reduces TAU Phosphorylation Independently of Amyloid Precursor Protein. Stem Cell Reports 10:1046-1058
Gallagher, Damien; Kiss, Alex; Lanctot, Krista et al. (2018) Depression and Risk of Alzheimer Dementia: A Longitudinal Analysis to Determine Predictors of Increased Risk among Older Adults with Depression. Am J Geriatr Psychiatry 26:819-827
Lin, Ming; Gong, Pinghua; Yang, Tao et al. (2018) Big Data Analytical Approaches to the NACC Dataset: Aiding Preclinical Trial Enrichment. Alzheimer Dis Assoc Disord 32:18-27
Haaksma, Miriam L; Calderón-Larrañaga, Amaia; Olde Rikkert, Marcel G M et al. (2018) Cognitive and functional progression in Alzheimer disease: A prediction model of latent classes. Int J Geriatr Psychiatry 33:1057-1064
Wang, Lucy Y; Raskind, Murray A; Wilkinson, Charles W et al. (2018) Associations between CSF cortisol and CSF norepinephrine in cognitively normal controls and patients with amnestic MCI and AD dementia. Int J Geriatr Psychiatry 33:763-768
Moreno, Monica A; Or-Geva, Noga; Aftab, Blake T et al. (2018) Molecular signature of Epstein-Barr virus infection in MS brain lesions. Neurol Neuroimmunol Neuroinflamm 5:e466
Blue, E E; Yu, C-E; Thornton, T A et al. (2018) Variants regulating ZBTB4 are associated with age-at-onset of Alzheimer's disease. Genes Brain Behav 17:e12429
Condello, Carlo; Lemmin, Thomas; Stöhr, Jan et al. (2018) Structural heterogeneity and intersubject variability of A? in familial and sporadic Alzheimer's disease. Proc Natl Acad Sci U S A 115:E782-E791
Goins, R Turner; Schure, Mark; Jensen, Paul N et al. (2018) Lower body functioning and correlates among older American Indians: The Cerebrovascular Disease and Its Consequences in American Indians Study. BMC Geriatr 18:6
Ramsey, Christine M; Gnjidic, Danijela; Agogo, George O et al. (2018) Longitudinal patterns of potentially inappropriate medication use following incident dementia diagnosis. Alzheimers Dement (N Y) 4:1-10

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