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Category:Autodesk softwareProject summary/abstract: Several human genetic studies have demonstrated a role for aging in the pathogenesis of Alzheimer’s disease (AD). Aging is associated with increased cognitive dysfunction, which is accelerated in AD patients. Studies in animal models suggest that the biological mechanisms responsible for the effects of aging in AD may include increased production of reactive oxygen species (ROS), reduced capacity of endogenous antioxidant defenses, and altered mitochondrial function. These studies also suggest that the genetic variability at mitochondrial-encoded complex I subunits and tau may be related to cognitive decline in healthy older adults and in AD. This proposal will utilize the special skills of the candidate in transgenic modeling of aging and AD to test the hypothesis that genetic variants at mitochondrial genes are associated with cognitive decline in older adults. The role of risk alleles in key genes, including PGC-1?, hTFAM, and tau, in determining risk of late-life cognitive decline and AD will be investigated in three specific aims. The candidate?s immediate career goal is to gain the training and experience necessary to develop an independent program of research in the field of aging, AD, and genetics. The proposed training will allow the candidate to 1) gain additional expertise in the fields of cellular and mitochondrial biology, aging research, and AD genetics and genetics of dementia; 2) develop skills and develop a knowledge base in aging research and genetic epidemiology; 3) develop a network of collaborators with complementary expertise; and 4) develop leadership and communication skills that will facilitate his development into an independent researcher. Finally, the proposed research will be conducted in an academic environment in a collaborative research team that has made several high impact discoveries related to the genetics of AD. The proposed research will be conducted in the laboratory of Dr. Elan
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