Temperature dependence of amyloid β-protein fibrillization

Abstract

Fibrillogenesis of the amyloid β-protein (Aβ) is believed to play a central role in the pathogenesis of Alzheimer’s disease. Previous studies of the kinetics of Aβ fibrillogenesis showed that the rate of fibril elongation is proportional to the concentration of monomers. We report here the study of the temperature dependence of the Aβ fibril elongation rate constant, k_e, in 0.1 M HCl. The rate of fibril elongation was measured at Aβ monomer concentrations ranging from 50 to 400 μM and at temperatures from 4°C to 40°C. Over this temperature range, k_e increases by two orders of magnitude. The temperature dependence of k_e follows the Arrhenius law, k_e = A exp (−E_A/kT). The preexponential factor A and the activation energy E_A are ≈6 × 10¹⁸ liter/(mol·sec) and 23 kcal/mol, respectively. Such a high value of E_A suggests that significant conformational changes are associated with the binding of Aβ monomers to fibril ends.