Affiliations: Department of Molecular and Cellular Biochemistry, Chandler School of Medicine and the Center on Aging, University of Kentucky, Lexington, KY, USA
Correspondence:
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Correspondence to: Harry Le Vine, III, 209 Sanders-Brown Building, 800 S. Limestone Street, Lexington, KY 40536-0230, USA. Tel.: +1 859 257 1412 X224; Fax: +1 859 323 2866; E-mail: hlevine@email.uky.edu.
Abstract: 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-β (Aβ) 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 Aβ peptide, inhibiting its aggregation, and promoting its removal, for example via immunotherapy. The success of anti-Aβ 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 Aβ peptide from the brain compartment. Little is known about exchange of theβ 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 Aβ peptide.
