Role of periodontal bacteria-derived dihydroceramides in Alzheimer's disease

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ABSTRACT This is an Independent Scientist Award (K02) application to the National Institute on Aging (NIA) from Dr. Alexandru Movila, Ph.D. who is an earlier stage investigator. Dr. Movila is an Assistant Professor in his third year appointment in the Department of Periodontology at Nova Southeastern University (NSU). Throughout his faculty career, Dr. Movila has established a strong publication record as an independent investigator in the field of oral inflammation induced by oral pathogens. His research is currently supported by R01AG064003, R03DE027153, and R15DE28699 grants addressing molecular mechanisms of ceramide lipids-induced periodontitis in relation to aging. Because the emerging evidence indicates that virulence factors secreted by periodontal pathogens may be engaged in initiation and/or progression of Alzheimer’s disease, the scientific goal of Dr. Movila is to establish a foundation of research for elucidation of pathogenic engagement of periodontal disease in the onset and progression of Alzheimer’s disease. Further, Dr. Movila’s long-term career goal is to become a leading basic research scientist in the field of aging and Alzheimer’s disease research. Currently, the PI has very limited experience in the pathophysiology of age-dependent neurodegenerative disease, including Alzheimer’s disease. However, due to the current workload at NSU that involve teaching and research mentoring of undergraduate and graduate dental students, he can only allocate a limited time for the research on Alzheimer’s disease associated with periodontitis. Thus, this career development KO2 award would provide the protected time to gain expertise in a new field of research. Based on his existing expertise in the oral pathogenesis and preliminary results, Dr. Movila hypothesized that ceramide lipid produced by the key periodontal pathogen Porphyromonas gingvalis, is engaged in Alzheimer’s disease pathogenesis via elevation of the hyper-phosphorylation of tau and amyloidogenic processing of amyloid precursor protein. The primary career development goals of this K02 application are: 1) to identify the possible pathogenic factors produced by periodontal pathogens that promotes progression of the Alzheimer’s disease pathology, 2) to receive hands-on training to learn the pre-clinical experimental mouse models of Alzheimer’s disease, 3) to establish academic collaborations with distinguished researchers in the fields; and 4) to build up academic credential in the Alzheimer disease research. The proposed career development training and research studies will help to Dr. Movila not only improving his knowledge and skill to study Alzheimer’s disease, but also increasing the network for collaborations and reputation in the field.