Alzheimer's Disease is characterized pathologically by two principal hallmark lesions: the senile plaque and the neurofibrillary tangle. Since the identification of each over 100 years ago, the major protein components have been elucidated. This has led in turn to the elaboration of metabolic cascades involving amyloid-Î² production in the case of the senile plaque, and phosphorylated-tau protein in the case of the neurofibrillary tangle. The pathogenesis and histogenesis of each have been the source of extensive investigation and some controversy in recent years, as both cascades have been implicated in the pathogenesis of Alzheimer's Disease, relied upon in the diagnostic criteria for Alzheimer's Disease at autopsy, and targeted for therapeutic intervention. With the accumulation of data and expansion of knowledge of the molecular biology of Alzheimer's Disease, it appears that the enthusiasm for successful intervention has been premature. In this book, we detail the discovery and characterization of the major pathological lesions, their associated molecular biology, their relationship to clinical disease, and potential fundamental errors in understanding that may be leading scientific investigators in unintended directions.
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Synopsis and Conclusion
About the Author(s)Rudy Castellani
, University of Maryland, School of Medicine
Dr. Rudolph J. Castellani is tenured professor of pathology and director of neuropathology at the University of Maryland School of Medicine. Dr. Castellani is the recipient of numerous awards for scientific merit, clinical service, and teaching, including the 2010 Alzheimer Medal, the 2011 Harlan I. Firminger award for excellence in pathology teaching, and Castle Connolly Medical Ltd. recognition as regional Top Doctor, 2013. His main fields of interest include neuropathology and pathogenesis of neurodegenerative diseases, prion diseases, and neurotrauma. He has published over 200 peer-reviewed papers, chapters, reviews, and books.George Perry
, University of Texas, San Antonio
George Perry, Ph.D., is Dean of the College of Sciences and Professor of Biology at the University of Texas at San Antonio. He obtained his Ph.D. from Scripps Institution of Oceanography in 1979 and received a postdoctoral fellowship in the Department of Cell Biology at Baylor College of Medicine where he laid the foundation for his observations of abnormalities in cell structures. Dr. Perry is distinguished as one of the top Alzheimer's Disease researchers with over 1,000 publications, one of the top 100 most-cited scientists in neuroscience and behavior, and one of the top 25 scientists in free radical research. He is editor for numerous journals and is editor-in-chief for the Journal of Alzheimer's Disease. Internationally recognized, he is a Foreign Correspondent Member of the Spanish Royal Academy of Sciences, the Academy of Science Lisbon, and a Foreign Member of the Mexican National Academy of Sciences. He is also a recent recipient of the National Plaque of Honor from the Republic of Panama Ministry of Science and Technology. Dr. Perry's research is primarily focused on how Alzheimer's Disease develops and the physiological consequences of the disease at a cellular level. He is currently working to determine the sequence of events leading to damage caused by and the source of increased oxygen radicals along with routes to provide more effective treatment.