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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AG034628-04
Application #
8318178
Study Section
Special Emphasis Panel (ZAG1-ZIJ-4 (M1))
Program Officer
Refolo, Lorenzo
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
4
Fiscal Year
2012
Total Cost
$108,000
Indirect Cost
$8,000
Name
University of California Los Angeles
Department
Neurology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
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Hsiao, Julia J; Lu, Po H; Grill, Joshua D et al. (2015) Longitudinal declines in instrumental activities of daily living in stable and progressive mild cognitive impairment. Dement Geriatr Cogn Disord 39:24-Dec
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