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
Kaur, Antarpreet; Edland, Steven D; Peavy, Guerry M (2018) The MoCA-Memory Index Score: An Efficient Alternative to Paragraph Recall for the Detection of Amnestic Mild Cognitive Impairment. Alzheimer Dis Assoc Disord 32:120-124
Taylor, Laura M; McMillan, Pamela J; Liachko, Nicole F et al. (2018) Pathological phosphorylation of tau and TDP-43 by TTBK1 and TTBK2 drives neurodegeneration. Mol Neurodegener 13:7
Flanagan, Margaret E; Larson, Eric B; Walker, Rod L et al. (2018) Associations between Use of Specific Analgesics and Concentrations of Amyloid-? 42 or Phospho-Tau in Regions of Human Cerebral Cortex. J Alzheimers Dis 61:653-662
Schaffert, Jeff; LoBue, Christian; White, Charles L et al. (2018) Traumatic brain injury history is associated with an earlier age of dementia onset in autopsy-confirmed Alzheimer's disease. Neuropsychology 32:410-416
Brenowitz, Willa D; Han, Fang; Kukull, Walter A et al. (2018) Treated hypothyroidism is associated with cerebrovascular disease but not Alzheimer's disease pathology in older adults. Neurobiol Aging 62:64-71
Tulloch, Jessica; Leong, Lesley; Thomson, Zachary et al. (2018) Glia-specific APOE epigenetic changes in the Alzheimer's disease brain. Brain Res 1698:179-186
Gallagher, Damien; Kiss, Alex; Lanctot, Krista L et al. (2018) Toward Prevention of Mild Cognitive Impairment in Older Adults With Depression: An Observational Study of Potentially Modifiable Risk Factors. J Clin Psychiatry 80:
Blue, Elizabeth E; Bis, Joshua C; Dorschner, Michael O et al. (2018) Genetic Variation in Genes Underlying Diverse Dementias May Explain a Small Proportion of Cases in the Alzheimer's Disease Sequencing Project. Dement Geriatr Cogn Disord 45:1-17
Gray, Shelly L; Anderson, Melissa L; Hanlon, Joseph T et al. (2018) Exposure to Strong Anticholinergic Medications and Dementia-Related Neuropathology in a Community-Based Autopsy Cohort. J Alzheimers Dis 65:607-616
Reed, May J; Damodarasamy, Mamatha; Pathan, Jasmine L et al. (2018) Increased Hyaluronan and TSG-6 in Association with Neuropathologic Changes of Alzheimer's Disease. J Alzheimers Dis :

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