Polymorphic Aβ42 fibrils adopt similar secondary structure but differ in cross-strand side chain stacking interactions within the same β-sheet

Agitation leads to formation of polymorphic Aβ42 fibrils

We used two conditions to prepare Aβ42 fibrils in PBS buffer (pH 7.4) at 37 °C: an agitated condition with orbital shaking at 600 rpm, and a quiescent condition without any agitation. Agitation has previously been used to make polymorphic Aβ40 fibrils^17,27,28. Transmission electron microscopy (TEM) studies show that Aβ42 formed long twisted fibrils under the quiescent condition, but short straight fibrils under agitated condition (Fig. 2, panels A and B). The agitated fibrils form bundles of laterally associated filaments. The quiescent fibrils are similar in morphology to other reported Aβ42 fibrils prepared in a neutral pH buffer without agitation¹⁵ or with slow rotation¹¹. The morphology of the agitated Aβ42 fibrils is similar to that of agitated Aβ40 fibrils, as previously reported by our group¹⁷ and by the…