My research in the Center is directed at determining amyloid precursor protein (APP) processing by neural cells in culture as a model system for the abnormal deposition of amyloid in the brain of Alzheimer’s disease patients. I have described with Fred Baskin, PhD, a platelet APP bio-marker that correlates in a linear manner with the severity of patient dementia . In 2003, it is being validated as a diagnostic test and severity index in a collaborative NIH study with eleven other Alzheimer’s Disease Centers in a study of 180 patients. In 2006, I published with K. Tang that human platelets utilize beta and gamma secretase to produce Abeta and that platelets from Alzheimer’s disease patients synthesize more Abeta than control platelets due to an increased activity of beta-secretase. Platelet Abeta levels may be an important bio-marker for Alzheimer’s disease and a means to monitor effectiveness of drug effect in clinical trials. In 2006, I published with Bao-Xi Qu and Stephan A. Johnston that a DNA Abeta42 gene vaccine can reduce Abeta42 levels in the brain of AD transgenic mice. A clinical trails with Alzheimer’s disease patients is being developed using this new DNA gene vaccination method.
My other major area of research is the molecular and clinical study of genetic neurological diseases. In that regard, I have been most active in studying the inherited ataxias including Machado-Joseph disease which I described initially with William Nyhan, M.D. Ph.D, in 1976. Our collaborative group mapped the chromosomal location of this disease to 14q24.3, and determined the molecular mutation causal of the disease in patients throughout the world (United States, Portugal, Canada, Japan, Brazil, Spain, France, England, China) is an increase in CAG unstable DNA triplet repeats which represents a novel, new mechanism of disease. CAG repeat levels in the MJD gene is now a comercially available bio-marker which has been shown to be effective in reducing the prevalence of this dominantly inherited spinocerebellar degeneration.
