An autocatalytic reaction as a model for the kinetics of the aggregation of β-amyloid

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Abstract

Alzheimer's disease is the commonest form of senile dementia, affecting almost 20 million people worldwide. This neurodegenerative disorder is characterized by amyloid deposition in senile plaques, composed primarily of fibrils of an aggregated peptide, β-amyloid. Fibrillation of β-amyloid is a nucleation-dependent polymerization process, which is controlled by two kinetics parameters: the nucleation rate and the elongation or growth rate. As the kinetics of fibrillation is strongly dependent on the presence of trace amounts of fibrils, we suggest that the aggregation of β-amyloid is a model of autocatalytic reaction. A mathematical analysis, permitting quantitative monitoring of the kinetics of fibrillogenesis of β-amyloid, nucleation, and elongation constants, is presented. The model was checked by applying it to the aggregation of the fragment 1–40 of the β-amyloid. Understanding of these rate constants may facilitate the study of the effect of substances used for controlling fibril creation and growth. The disaggregating effect of dodecyl trimethylammonium bromide, a cationic surfactant, was easily quantified by means of the model. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 71:190–195, 2003

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