Direct Nanospectroscopic Verification of the Amyloid Aggregation Pathway. Issue 28 (6th June 2018)

• Record Type: Journal Article
• Authors: Lipiec, Ewelina; Perez‐Guaita, David; Kaderli, Janina; Wood, Bayden R.; Zenobi, Renato
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 28(2018)
• Page Start: 8519
• Page End: 8524
• Publication Date: 2018-06-06
• Subjects: Alzheimer's disease -- protein aggregation pathway -- secondary structure -- tip-enhanced Raman spectroscopy -- β-amyloid; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201803234
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The aggregation pathways of neurodegenerative peptides determine the disease etiology, and their better understanding can lead to strategies for early disease treatment. Previous research has allowed modelling of hypothetic aggregation pathways. However, their direct experimental observation has been elusive owing to methodological limitations. Herein, we demonstrate that nanoscale chemical mapping by tip‐enhanced Raman spectroscopy of single amyloid fibrils at various stages of aggregation captures the fibril formation process. We identify changes in TERS/Raman marker bands for Aβ1‐42, including the amide III band (above 1255 cm −1 for turns/random coil and below 1255 cm −1 for β‐sheet conformation). The spatial distribution of β‐sheets in aggregates is determined, allowing verification of a particular fibrillogenesis pathway, starting from aggregation of monomers to meta ‐stable oligomers, which then rearrange to ordered β‐sheets, already at the oligomeric or protofibrillar stage. Abstract : A TERS observation : Tip‐enhanced Raman spectroscopy of single amyloid‐β fibrils at various stages of aggregation captures the fibril formation process. The spatial distribution of β‐sheets in aggregates was determined based on amide III band position, allowing verification of a fibrillogenesis pathway, from aggregation of monomers to metastable oligomers, which then rearrange into ordered β‐sheets, already at the oligomeric or protofibrillar stage.