Amyloid Beta Aggregation in the Presence of Temperature-Sensitive Polymers

The formation of amyloid fibrils is considered to be one of the main causes for many neurodegenerative diseases, such as Alzheimer's, Parkinson's or Huntington's disease. Current knowledge suggests that amyloid-aggregation represents a nucleation-dependent aggregation process in vitro, where a sigmoidal growth phase follows an induction period. Here, we studied the fibrillation of amyloid β 1-40 (Aβ₄₀) in the presence of thermoresponsive polymers, expected to alter the Aβ₄₀ fibrillation kinetics due to their lower critical solution behavior. To probe the influence of molecular weight and the end groups of the polymer on its lower critical solution temperature (LCST), also considering its concentration dependence in the presence of buffer-salts needed for the aggregation studies of the amyloids, poly(oxazolines) (POx) with LCSTs ranging from 14.2⁻49.8 °C and poly(methoxy di(ethylene glycol)acrylates) with LCSTs ranging from 34.4⁻52.7 °C were synthesized. The two different polymers allowed the comparison of the influence of different molecular structures onto the fibrillation process. Mixtures of Aβ₄₀ with these polymers in varying concentrations were studied via time-dependent measurements of the thioflavin T (ThT) fluorescence. The studies revealed that amyloid fibrillation was accelerated in, accompanied by an extension of the lag phase of Aβ₄₀ fibrillation from 18.3 h in the absence to 19.3 h in the presence of the poly(methoxy di(ethylene glycol)acrylate) (3600 g/mol).