In Vitro Fibrillization Of Alzheimer'S Amyloid-Beta Peptide (1-42)

The amyloid deposition in the form of extracellular fibrillar aggregates of amyloid-beta (A beta) peptide is a critical pathological event in Alzheimer's disease. Here, we report a systematic investigation of the effects of environmental factors on the kinetics of A beta fibrillization in vitro. The effects of A beta 42 peptide concentration, temperature, pH, added solvents and the ratio of A beta 40 and A beta 42 on the peptide fibrillization under agitated conditions was studied. The analysis show that the rate of fibril growth by monomer addition is not limited by diffusion but by rearrangement in the monomer structure, which is enhanced by low concentrations of fluorinated alcohols and characterized by the activation energy of 12 kcal/ mol. Fibrillization rate decreases at pH values below 7.0 where simultaneous protonation of His 13 and 14 inhibits fibril formation. The lag period for A beta 42 was only twofold shorter and the fibril growth rate twofold faster than those of A beta 40. Lag period was shortened and the fibrillization rate was increased only at 90% content of A beta 42. (C) 2015 Author(s).