This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Alzheimer's disease (AD) is a progressive, neurodegenerative disorder, characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions. Synaptic damage and mitochondrial oxidative damage have been reported as early events in Alzheimer's disease. Recently, our laboratory found amyloid beta in mitochondrial membranes in neurons from Alzheimer's disease transgenic mice and Alzheimer's disease postmortem brains. Mitochondrial associated amyloid beta species were found to interact with mitochondrial proteins, disrupt mitochondrial function and prevent neurons from functioning normally. Based on abnormal interaction of amyloid beta with mitochondrial proteins in Alzheimer's disease neurons, several studies suggest that mitochondrial targeted therapeutic interventions protect Alzheimer's disease neurons, and may be effective in delaying Alzheimer's disease progression in elderly individuals and in treating Alzheimer's disease patients. Recently, several mitochondrial-targeted drugs have been developed, and these targeted boost mitochondrial function. We investigated the efficacies of these drugs in nerve cells in culture. Our initial studies found that deceased levels of free radicals and increased mitochondrial function, indicating that these mitochondrial targeted drugs have neuroprotective properties. However, no studies have investigated thus far to determine the efficacies of these drugs in Alzheimer's disease mice. Therefore, we hypothesized that 1). Mitochondrial targeted drugs effectively neutralizes mitochondrial free radicals, decreases oxidative damage, and protects neurons from amyloid beta and mitochondrial toxicity, and 2) we also hypothesize that mitochondrial targeted drugs decreases Alzheimer's disease pathology, and ameliorates cognitive behavioral deficits in Alzheimer's disease mice. In this present project, we are determining the mitochondrial function and amyloid beta pathology.

National Institute of Health (NIH)
National Center for Research Resources (NCRR)
Primate Research Center Grants (P51)
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Special Emphasis Panel (ZRR1-CM-8 (01))
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Oregon Health and Science University
Schools of Medicine
United States
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