Aggregation process of Aβ1-40 with non-Aβ amyloid component of α-synuclein

Many neurodegenerative diseases, such as Alzheimer’s and Parkinson’s diseases, are characterized by the presence of amyloid fibers. Recently, attention has turned from the fibers to the early stages of oligomerization where toxicity could be highest. Here, we focus on the interactions between non-Aβ amyloid component of α-synuclein (NAC) and Aβ1−40, two proteins found in amyloid fibrils associated with Alzheimer’s disease. We combine the coarse-grained OPEP potential with a Hamiltonian and temperature replica exchange molecular dynamics simulation (HT-REMD) to identify mechanisms leading to the formation of secondary structures promoting fibrillation. We observe that the propensity to form beta-sheet remains the same for Aβ1−40 whereas is decreases significantly for NAC. In particular, the 25-35 region of Aβ1−40 is a significant area of secondary structure stabilization with NAC. The ionic interactions between salt-bridge D23 and K28 in Aβ1−40 and K20 and E23 in NAC of the heterogeneous dimer are consistent with the salt-bridges found in NAC and Aβ1−40 homogenous dimers and allow us to see that these interactions don’t necessarily dominate the interchain stabilizations. Our numerical simulation also show the formation of interaction between the early oligomer of NAC and Aβ1−40.