This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kim, J. R. Articles by Murphy, R. M. Search for Related Content PubMed PubMed Citation Articles by Kim, J. R. Articles by Murphy, R. M.

Mechanism of Accelerated Assembly of ß-Amyloid Filaments into Fibrils by KLVFFK₆

Department of Chemical and Biological Engineering, University of Wisconsin, Madison, Wisconsin

Correspondence: Address reprint requests to Dr. Regina M. Murphy, Dept. of Chemical and Biological Engineering, University of Wisconsin, 1415 Engineering Dr., Madison, WI 53706. Tel: 608-262-1587; Fax: 608-262-5434; E-mail: murphy{at}che.wisc.edu.

Extracellular senile plaques are a central pathological feature of Alzheimer's disease. At the core of these plaques are fibrillar deposits of ß-amyloid peptide (Aß). In vitro, Aß spontaneously assembles into amyloid fibrils of cross-ß sheet structure. Although it was once believed that the fibrils themselves were toxic, more recent data supports the hypothesis that aggregation intermediates, rather than fully formed fibrils, are the most damaging to neuronal tissue. In previously published work, we identified several small peptides that interact with Aß and increase its aggregation rate while decreasing its toxicity. In this work, we examined in detail the interaction between Aß and one of these peptides. Using a mathematical model of Aß aggregation kinetics, we show that the dominant effect of the peptide is to accelerate lateral association of Aß filaments into fibrils.