Nanoscale infrared spectroscopy identifies parallel to antiparallel beta sheet transformation of Aβ fibrils

Abstract

Spontaneous aggregation of amyloid beta proteins leading to the formation of oligomers and eventually into fibrils has been identified as a key pathological signature of Alzheimers disease. Structure of late stage aggregates have been studied in depth by conventional structural biology techniques including Nuclear Magnetic Resonance, X-ray crystallography and Infrared Spectroscopy; however the structure of early-stage aggregates is less known due to their transient nature. As a result, the structural evolution of amyloid aggregates from its early oligomers to mature fibril is still not fully understood. Here we have applied AFM-IR nanospectroscopy to investigate the aggregation of amyloid beta 16-22, which spans the amyloidogenic core of the amyloid beta peptide. Our results demonstrate that amyloid beta 16-22 involves a structural transition from oligomers with parallel beta sheets to antiparallel fibrils through disordered and possibly helical intermediate fibril structures, contrary to the known aggregation pathway of full-length amyloid beta 42.