Suzanne S. Mirra, MD - US grants

The Alzheimer's Disease Center Core (ADCC) will build upon and enhance the resources available at Emory to create a foundation upon which research on Alzheimer's disease (AD) will grow. To facilitate this growth, clinical and research activities on the Emory Campus, nearby Wesley Woods and VA Medical Centers, as well as Grady Memorial Hospital in downtown Atlanta have been coordinated. The Administrative Core is organized to foster a collegial and stimulating environment with maximum interaction of ADCC and other investigators. In a setting of quality patient care and family support, the Clinical Core will provide a well characterized population of AD patients and cognitively normal individuals thus creating a comprehensive database from which clinical, epidemiological, and basic scientific studies will emanate. Proactive minority outreach will be emphasized by clinical and educational initiatives in cooperation with community and other groups. Capitalizing upon the strengths and interests of Emory faculty in the genetics and biochemistry of oxidative phosphorylation (OXPHOS) and oxygen radical damage to DNA and its repair, we have added a Molecular Biology Core to the ADCC. This core will assist in the metabolic and genetic characterization of AD patients and control subjects of varying age and provide new opportunities for AD research. The Neuropathology Core will supply brain and other appropriate tissues from well characterized dementia and control cases to the Molecular Core and to other investigators through maintenance of an active brain bank for acquisition, storage, handling, and distribution of tissue. Neuropathological information will be pooled with clinical and biochemical and genetic data to provide a sound base for clinical and basic scientific investigations. Participation of epidemiologists and biostatisticians from the Emory School of Public Health will support ADCC study design and analysis. The Education and Information Transfer Core will provide innovative programs for professionals caregivers and other lay groups. In combination with strong institutional and community support, the Emory ADCC will be catalyst for new research in AD.

The CERAD Neuropathology Task Force will refine and improve the CERAD neuropathology protocol from the standardized, reliable, and practical evaluation of autopsy brains from dementia and control subjects. A long range goal is to improve the quality of the neuropathology assessment of autopsy brains from demented patients by neuropathologists and non- specialist pathologists. Our revised data entry form and illustrated guidebook will facilitate inclusion of information on a broad spectrum of pathological changes associated with AD. Analysis of the data will lead to development of more accurate and reliable neuropathological criteria, characterization of clinical-pathological subsets, and understanding of the range of changes in AD. Clinical-pathological correlation on CERAD subjects will be emphasized by correlating neuropathology data with clinical and neuropsychological information on demented and control subjects. Issues such as the relationship of extrapyramidal signs and Parkinson's disease changes in AD, the spectra of Parkinson's disease related disorders such as diffuse Lewy body disease, as well as the nature and frequency of AD and its neuropathological basis will be explored. To insure quality control of the CERAD neuropathology assessment, we have instituted several procedures, including an external blinded review of slides without clinical history, and distribution of unknown slides to measure agreement and inter-rater reliability among neuropathologists with regard to diagnoses and histopathological features.

The Neuropathology Core will facilitate research on Alzheimer's disease (AD) by providing diagnostic and comprehensive neuropathological assessment on autopsy brains from well characterized patients and control subjects. Particular emphasis will be placed on characterization of the neuropathological heterogeneity of AD and its overlap with Parkinson's disease and other neurodegenerative disorders. Information on the neuropathological basis of dementia in the understudied African American population will be sought as clinical and educational outreach programs of the Alzheimer's Disease Center emphasize the importance of the autopsy. Through the maintenance of a 24 hour autopsy service and brain bank, the Neuropathology Core will supply brain tissue and other materials to the growing number of investigators at Emory involved in ongoing and new research studies. Neuropathology information will be maintained in a secure data base and integrated with data generated by the Clinical and Molecular Biology Cores.

The overall goal of this Academic Career Leadership Award is to develop an outstanding research and educational program on Alzheimer's disease (AD) and other neurodegenerative disorders at the State University of New York, Health Science Center at Brooklyn (Downstate). We plan to build upon the existing strengths at Downstate and the unique demographics of its surrounding community. These include the neuroscience program with its emphasis on hippocampal pathophysiology, the large population of Caribbean American, African American, and other minority groups in Brooklyn, and the special interests of the PI, including the overlap and heterogeneity of AD, Parkinson's disease and other neurodegenerative disorders. Our specific aims are to (1) establish an infrastructure to support the development of an institutional research center on AD and related neurodegenerative disorders; (2) develop mechanisms that will bring new investigators to the field, enable established investigators to channel their expertise towards the field, encourage collaborations, and support pilot studies; (3) stimulate interest and collaborations in AD-related research within the scientific community through educational programs and related experiences; and (4) promote awareness of AD in the lay and professional community through outreach and educational programs. The candidate, Dr. Suzanne Mirra, is well qualified to lead this initiative. An experienced and respected neuropathologist working on AD and other neurodegenerative disorders, Dr. Mirra was the director and principal investigator of the Alzheimer's Disease Center at her former institution. She led the neuropathology arm of CERAD (Consortium to Establish a Registry for AD), the NIA longitudinal study, in standardizing the neuropathological evaluation of AD. A nationally recognized leader in neuropathology, she is Founding Chair of the Neuropathology Committee of the College of American Pathologists and President-Elect of the American Association of Neuropathologists. Dr. Mirra has forged strong ties in the lay community, such as her involvement with the national board and regional chapters of the Alzheimer's Association. Moreover, she is an outstanding communicator as well as a committed and innovative educator with a demonstrated track record of outreach to non-white minorities. This Academic Career Leadership Award, along with strong institutional commitment, will enable Dr. Mirra and collaborators to build a thriving research program on Alzheimer's disease and related neurodegenerative disorders at Downstate.