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The abnormal accumulation of a small protein called ß-amyloid is believed to play an early and critical role in the development of Alzheimer's disease (AD). There are two predominant forms of ß-amyloid found in AD brain: ß-amyloid 40 and ß-amyloid 42. ß-amyloid 42 is the more toxic form and is selectively elevated in many people that have genetic mutations that cause Alzheimer's disease. Dr. Eckman and his colleagues have recently developed high throughput screens that allow them to search for candidate drugs that effect total ß-amyloid levels in parallel with those that selectively effect either ß-amyloid 40 or ß-amyloid 42. They have begun to utilize this assay to screen for natural product extracts that influence ß-amyloid accumulation. Using this approach, they have already identified one natural product extract that is capable of the selective reduction of ß-amyloid 42. To date, this is the only lead reported which selectively reduces ß-amyloid 42 and may represent a novel class of drugs that specifically target this more toxic ß-amyloid species. Dr. Eckman proposes to further evaluate this extract in an animal model of AD to determine if it can if it can prevent amyloid deposition. In addition they will screen the remainder of the natural product library in a search for other anti-beta-amyloid drugs.