Discussion about Alzheimer's

January 12, 1999

Alzheimer's disease Panel Discussion with guests Jim Geddes, Ph.D, Mark Gurney, Ph.D., Ole Isacson, M.D, and Li-Huei Tsai, Ph.D.

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Bio Online: Welcome to Chat with Bio Online! This evening we have the chance to learn about the latest discoveries in Alzheimer's disease research from the pioneers themselves!

Jim Geddes, Ph.D.: Hello. I am Jim Geddes, the moderator for tonight's chat. Over the next hour, scientists responsible for important recent findings in Alzheimer's research will discuss their techniques. We will be able to hear about their interesting work and then ask questions. First, I think it's important to provide a brief background on Alzheimer's Disease, a progressive attack on specific brain regions, resulting in impaired memory and behavior. By the age of 85, Alzheimer's disease affects 1 in 3 individuals. In roughly 7 of the cases, Alzheimer's disease is caused by gene mutations. In the remaining individuals, the cause of Alzheimer's disease is not known, although risk factors have been identified. The brain of an individual with Alzheimer's disease contains two abnormal structures, senile plaques and neurofibrillary tangles. Senile plaques are composed of aggregates of the beta-amyloid protein, formed by the cleavage of amyloid precursor protein by distinct proteases called beta- and gamma-secretase. Neurofibrillary tangles consist of aggregates of excessively phosphorylated tau protein. There has been considerable debate regarding the critical role of beta-amyloid vs. tau, with a growing consensus that both proteins are important players in the disease. We are very fortunate to have a distinguished panel of scientists with us today, each of whom has made highly significant recent discoveries regarding mechanisms underlying the changes that occur in the Alzheimer's disease brain. Before I present our expert and noted panel, I would like to introduce myself. I'm Jim Geddes, Ph.D., Director, Spinal Cord and Brain Injury Research Center, University of Kentucky, Editor of Alzheimer's Disease Review, and Review Editor of the Journal of Alzheimer's Disease. With us for this next hour, we are honored to have - Mark E. Gurney, Ph.D., Senior Scientist, Biology II/Neurobiology from Pharmacia & Upjohn, Inc. Ole Isacson, M.D., Director, Neuroregeneration Laboratory, McLean Hospital, Associate Professor of Neurology, Harvard Medical School Jeff Kuret, Ph.D., Associate Professor, Department of Medical Biochemistry, Ohio State University, and, Li-Huei Tsai, Ph.D., Associate Professor of Pathology, Department of Pathology Harvard Medical School, Assistant Investigator, Howard Hughes Medical Institute Why don't we begin by having each of our panelists briefly describe their latest findings, and explain the impact they will have on further Alzheimer's disease research.

Mark Gurney, Ph.D.: Thank you very much, Dr. Geddes. We and a number of other groups around the world recently reported the cloning of an important enzyme in the area of Alzheimer's disease research. One of the enzymes that cleaves the A-beta heptide from the amyloid protein precursor. There are two enzymes responsible for cleaving the peptoid. These are called the beta and gamma secretase. We and others recently cloned the beta secretase. This is a novel membrane anchored aspartyl protea.

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