Nanoscale Infrared Spectroscopy Identifies Structural Heterogeneity in Individual Amyloid Fibrils and Prefibrillar Aggregates

被引：16

作者：

Banerjee, Siddhartha ^{[1
]}

Holcombe, Brooke ^{[1
]}

Ringold, Sydney ^{[1
]}

Foes, Abigail ^{[1
]}

Naik, Tanmayee ^{[1
]}

Baghel, Divya ^{[1
]}

Ghosh, Ayanjeet ^{[1
]}

机构：

[1] Univ Alabama, Dept Chem & Biochem, Tuscaloosa, AL 35487 USA

来源：

JOURNAL OF PHYSICAL CHEMISTRY B | 2022年 / 126卷 / 31期

基金：

美国国家卫生研究院;

关键词：

ATOMIC-RESOLUTION STRUCTURE; ANTIPARALLEL BETA-SHEET; OFF-PATHWAY OLIGOMERS; ALZHEIMERS-DISEASE; A-BETA; SECONDARY STRUCTURE; AMYLOID-BETA(1-42); POLYMORPHISM; A-BETA(1-42); SIGNATURE;

D O I：

10.1021/acs.jpcb.2c04797

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Amyloid plaques are one of the central manifestations of Alzheimer's disease pathology. Aggregation of the amyloid beta (A beta) protein from amorphous oligomeric species to mature fibrils has been extensively studied. However, structural heterogeneities in prefibrillar species, and how that affects the structure of later-stage aggregates are not yet well understood. The integration of infrared spectroscopy with atomic force microscopy (AFM-IR) allows for identifying the signatures of individual nanoscale aggregates by spatially resolving spectra. We use AFM-IR to demonstrate that amyloid oligomers exhibit significant structural variations as evidenced in their infrared spectra. This heterogeneity is transmitted to and retained in protofibrils and fibrils. We show that amyloid fibrils do not always conform to their putative ordered structure and structurally different domains exist in the same fibril. We further demonstrate that these structural heterogeneities manifest themselves as a lack of beta sheet structure in amyloid plaques in Alzheimer's tissue using infrared imaging.

引用

页码：5832 / 5841

页数：10

共 73 条

[1] Structural conversion of neurotoxic amyloid-β1-42 oligomers to fibrils [J].