The Amyloid Hypothesis and the clearance and degradation of Alzheimer's beta-peptide.
The second generation of therapeutic strategies for Alzheimer's disease (AD) embraces the Amyloid Hypothesis, which asserts that through a series of events not completely understood, misfolding of the amyloid-beta (Abeta) peptide is a primary event eliciting neurodegeneration and AD pathology. A variety of approaches are being tried to interrupt the disease process, including reducing the production of the Abeta peptide, inhibiting its aggregation, and promoting its removal, for example via immunotherapy. The success of anti-Abeta disease-modifying approaches in eliminating the postulated etiologic form(s) of the peptide will ultimately depend on biological clearance and degradation of the various forms of the Abeta peptide from the brain compartment. Little is known about exchange of the Abeta peptide between the brain and blood. Increased understanding of this process in experimental animal models and humans, and how it changes with aging, will likely open new therapeutic avenues. It will also be needed to properly design early clinical trials to verify the efficacy of potential drug candidates working through the Abeta peptide.
LeVine
Harry
H
Department of Molecular and Cellular Biochemistry, Chandler School of Medicine and the Center on Aging, University of Kentucky, Lexington, KY, USA. hlevine@email.uky.edu
D000375:Aging / Q000502:physiology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D006801:Humans; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D010447:Peptide Hydrolases / Q000494:pharmacology / Q000627:therapeutic use
D016564:Amyloid beta-Protein Precursor; D010447:Peptide Hydrolases