My prior research background has involved the assessment of cognitive, behavioral and functional deficits associated with memory impairment in both animal models and human populations. My current and long- term career goals are focused upon developing a translational research program that uses biochemical markers to accelerate the discovery of new therapies for Alzheimer's disease (AD). The career development plan described in this application will facilitate my achievement of these goals by allowing me to obtain greater technical expertise with the biochemical and pharmacological aspects of AD through the acquisition of new research skills in the laboratory of Dr. Gregory Cole at the Greater Los Angeles Veterans Affairs Healthcare System, and a more comprehensive understanding of the AD drug discovery through the completion of formal coursework in clinical pharmacology and clinical trials methodology at UCLA. This career development plan will be complemented by the proposed research project, which seeks to determine whether an transgenic rat model of AD can be used to determine the utility of longitudinal measurements of two potential biological markers of AD in the cerebrospinal fluid (CSF), beta-amyloid 1-42 (AP42) and phosphorylated tau (p-tau) for the assessment of disease progression and response to treatment at early stages of the disease. We hypothesize that the levels of these markers will change in conjunction with age- associated increases in disease progression. We further hypothesize that these changes will be differentially modulated by treatment with curcumin or docosahexaenoic acid (DMA) and will be affected by both the duration of treatment and the severity of disease at the time of treatment. The use of curcumin and DHA, which have demonstrated efficacy in reducing disease progression in other animal models and have distinct underlying mechanisms, will allow us to assess how successful therapies affect these putative CSF biomarkers of AD. The results of this study will clarify the roles of CSF Ap42 and p-tau in clinical trials of AD therapeutics and form the basis for future studies of other potential CSF biomarkers and other potential therapeutic treatments in this promising animal model system.
This project has the potential to help develop more efficient methods for identifying promising medications for AD that result in clinical trials that take less time and money to complete. Facilitating the development of more effective medications for AD is of critical importance to the NIA given the elevated prevalence of this disease in the rapidly growing elderly populations of the United States and other industrialized countries.
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