Nanoscale Infrared Spectroscopy Identifies Parallel to Antiparallel β-Sheet Transformation of Aβ Fibrils
Siddhartha Banerjee, Divya Baghel, Md Hasan Ul Iqbal, Ayanjeet Ghosh
Abstract
Spontaneous aggregation of amyloid beta (Aβ) proteins leading to the formation of oligomers and eventually into fibrils has been identified as a key pathological signature of Alzheimer's disease. The 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 early oligomers to mature fibrils is still not fully understood. Here, we have applied atomic force microscopy-infrared nanospectroscopy to investigate the aggregation of Aβ 16-22, which spans the amyloidogenic core of the Aβ peptide. Our results demonstrate that Aβ 16-22 involves a structural transition from oligomers with parallel β-sheets to antiparallel fibrils through disordered and possibly helical intermediate fibril structures, contrary to the known aggregation pathway of full-length Aβ.