Temperature dependence of the nucleation constant rate in beta amyloid fibrillogenesis.

Beta-amyloid peptide (A beta), in fibrillar form, is the primary constituent of senile plaques, a defining feature of Alzheimer's disease (AD). In solution assays, fibrils form with a lag time, interpreted as a nucleation/condensation-dependent process. The kinetics of fibrillogenesis is controlled by two key parameters: nucleation and elongation rate constants. We report here the study of the temperature dependence of the nucleation rate constant on an A beta monomer concentration of 18.4 microM at pH 7.4 and at temperatures ranging from 302 to 318 K. We found that the nucleation constant varied as in the Arrhenius law, giving an activation energy of 311.2 kJ mol(-1). The corresponding values of enthalpy of activation (deltaH*), entropy of activation (deltaS*) and Gibbs energy of activation (deltaG*) were evaluated by Eyring's equation of absolute reaction rate. A Gibbs energy of activation of approximately 110 kJ mol(-1) was obtained.

Physical stability of liposomes bearing hemostatic activity.

The physical stability of six liposome systems designed as platelet substitutes was determined on storage at 4 degrees C over a 3-month period under quiescent conditions. Liposomes used were large unilamellar vesicles. Correlation of the n-average mean diameter, polydispersity, zeta-potential and the presence of aminophospholipid on liposome surface (in those preparations which contain phosphatidylethanolamine (PE) and phosphatidylserine (PS)) led to the conclusion that liposomes that mimicked the composition of platelets were the most stable. When a net charge was present in the vesicles (liposomes with PS), the likelihood of aggregation was extremely low. In the period studied, a proportion of 25% of charged lipid (PS) conferred sufficient electrostatic stabilization to prevent vesicle fusion. An increase in this charge did not modify the stability characteristics. PE-containing liposomes behaved in a particular way: when PE content was 50%, the stability of the preparation was limited to 1 month; whereas if the content was 25%, the zeta-potential rose with time, as did the presence of PE in the liposome surface.

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

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, beta-amyloid. Fibrillation of beta-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 beta-amyloid is a model of autocatalytic reaction. A mathematical analysis, permitting quantitative monitoring of the kinetics of fibrillogenesis of beta-amyloid, nucleation, and elongation constants, is presented. The model was checked by applying it to the aggregation of the fragment 1-40 of the beta-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.