pH Dependence of Amyloid‐β Fibril Assembly Kinetics: Unravelling the Microscopic Molecular Processes

Central to Alzheimer's disease (AD) is the assembly of amyloid-beta peptide (Aβ) into fibrils. A reduction in pH accompanying inflammation or subcellular compartments, may accelerate fibril formation as approaches Aβ’s isoelectric point (pI). Using global fitting kinetics over a range pHs, we identify impact net charge has on individual microscopic rate constants. We show that primary nucleation strong dependence. The titration behaviour exhibits mid-point pKa 7.0, close Aβ histidine imidazoles. Surprisingly, both secondary and elongation constants are independent. This indicates Aβ, particular protonation, little this stage assembly. These fundamental processes key understanding forces drive toxic oligomers