Abstract
Amyloid-β (Aβ) fibril formation is the pivotal phenomenon in Alzheimer's disease (AD). However, the understanding of amyloid fibril mechanism has been hindered by its heterogeneous morphology. Further, recent studies point out the existence of new growth sites on pre-existing fibrils, called secondary nucleation, but there is no report of secondary nucleation for Aβ 42. Here we present a detailed inter-conversion scheme of Aβ42 from the study of Aβ fibrillogenesis by means of electron microscopy and atomic force microscopy. We indentified that the secondary nucleation events occur more favorably on specific fibril type during monomer fibrillization. Further, we proved the stability of the most homogeneous and stable Aβ42 fibril type and analyzed the structural elastic properties by using the statistical theory of semi-flexible polymer. The result suggests that lateral association mechanism gives the most structural stability to certain fibril type with a twisted ribbon structure. The extracted elastic modulus of fibrils is ∼ 1.4 GPa on mica and highly ordered pyrolytic graphite. We suggest that elucidation of secondary nucleation events and elastic modulus value will help progress in our understanding of the aggregation mechanism of Aβ 42 fibrillogenesis in AD.
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