Dependence of the Formation of Tau and Aβ Peptide Mixed Aggregates on the Secondary Structure of the N-Terminal Region of Aβ.

One of the hallmarks of Alzheimer's disease is the formation of aggregates of the tau protein, a process that can be facilitated by the presence of fibrils formed by the amyloid β peptide (Aβ). However, the mechanism that triggers tau aggregation is still a matter of debate. The effect of Aβ fibrils on the aggregation of the repeat domain of tau (TauRD) is investigated here by employing coarse-grained molecular dynamics simulations. The results indicate that the repeat domain of tau has a high affinity for Aβ fibrils, with the GSTENLK fragment of tau driving TauRD toward the KLVFFA fragment in Aβ. Monomeric Aβ, in which the KLVFFA fragment is rarely found in an extended conformation (as in the fibril), has a low affinity for the TauRD, indicating that the ability of Aβ fibrils to bind to the TauRD depends on the KLVFFA fragment of Aβ adopting an extended conformation.