TEMPERATURE-DEPENDENCE OF AMYLOID BETA-PROTEIN FIBRILLIZATION

Fibrillogenesis of the amyloid beta-protein (A beta) is believed to pl ay a central role in the pathogenesis of Alzheimer's disease. Previous studies of the kinetics of A beta fibrillogenesis showed that the rat e of fibril elongation is proportional to the concentration of monomer s. We report here the study of the temperature dependence of the A bet a fibril elongation rate constant, k(e), in 0.1M HCl. The rate of fibr il elongation was measured at A beta monomer concentrations ranging fr om 50 to 400 mu M and at temperatures from 4 degrees C to 40 degrees C . Over this temperature range, k(c) increases by two orders of magnitu de. The temperature dependence of k(e) follows the Arrhenius law, k(e) = A exp (-E-A/kT), The preexponential factor A and the activation ene rgy E-A are approximate to 6 x 10(18) liter/(mol.sec) and 23 kcal/mol, respectively. Such a high value of E-A suggests that significant conf ormational changes are associated with the binding of AP monomers to f ibril ends.