Identifying Polymorphs of Amyloid-β (1-40) Fibrils Using High-Resolution Atomic Force Microscopy

Many amyloid-β fibril preparations are highly polymorphic, and the conditions under which they form determine their morphology. This report describes the application of high-resolution atomic force microscopy, combined with volume-per-length analysis, to define, identify, and quantify the structural components of polymorphic Aβ fibril preparations. Volume-per-length analysis confirms that they are composed of discrete cross-β filaments, and the analysis of high-resolution atomic force microscopy images yields the number of striations in each fibril. Compared to mass-per-length analysis by electron microscopy, high-resolution atomic force microscopy analysis yields narrower distributions, facilitating rapid and label-free quantitative morphological characterization of Aβ fibril preparations.