Identifying Terminal Assembly Propensity Of Amyloidal Peptides By Scanning Tunneling Microscopy

The abnormal accumulation of beta-amyloids (A beta) in brain is considered as a key initiating cause for Alzheimer's disease (AD) due to their richness in plaques and self-aggregate propensity. In recent studies, N-terminally extended A beta peptides (NTE-A beta) with the N-terminus originating prior to the canonical beta-secretase cleavage site were found in humans and suggested to have possible relevance to AD. However, the effects of the extended N-terminus on the amyloidegenic structure and aggregation propensity have not been fully elucidated. Herein, we characterized the assembly structures of A beta 1-42, A beta(-5)-42, A beta(-10)-42 and A beta(-15)-42 with both normal and reversed sequences on highly oriented pyrolytic graphite (HOPG) surfaces with scanning tunneling microscopy (STM). The molecularly resolved surface-mediated peptide assemblies enable identification of amyloidegenic fragments. The observations reveal that the assembly propensity of the C-terminal strand of A beta 1-42 is highly conserved and insensitive to N-terminal extensions. In contrast, different assembly structures of the N-terminal strand of A beta variants can be observed with possible assignment of varied amyloidegenic fragments in the extended N-termini, which may contribute to the varied aggregation propensities of A beta 42 species.