3D Blockage Mapping for Identifying Familial Point Mutations in Single Amyloid‐β Peptides with a Nanopore

• Published in: Angewandte Chemie Vol. 134; no. 44
• Main Authors: Xin, Kai‐Li, Hu, Zheng‐Li, Liu, Shao‐Chuang, Li, Xin‐Yi, Li, Jun‐Ge, Niu, Hongyan, Ying, Yi‐Lun, Long, Yi‐Tao
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 02.11.2022
• Subjects: 3D Blockage Mapping; Aerolysin Nanopore; Alzheimer's disease; Amyloid-β Peptides; Chemistry; Familial Alzheimer's Disease; Mutants; Mutation; Neurodegenerative diseases; Peptide mapping; Peptides; Single Amino Acid Mutations; β-Amyloid
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202209970

Accurate discrimination of amyloid‐β (Aβ) peptides containing familial point mutations would advance the knowledge of their roles in early‐onset Alzheimer's disease. Herein, we simultaneously identified the mutant A21G, E22G, E22Q, and the wild‐type (WT) Aβ18–26 peptides with aerolysin nanopore using a 3D blockage mapping strategy. The standard deviation of current blockade fluctuations (σb) was proposed as a new supplement to current blockage (Ib/I0) and duration time (tD) to profile the blockage characteristics of single molecules. Although the WT and A21G Aβ18‐26 are indistinguishable in a traditional Ib/I0‐tD 2D description, ∼87 % of the blockade events can be accurately classified with half reduction of false identification using a combination of Ib/I0, tD, and σb. This work offers an easy and reliable strategy to promote nanopore sensitivity of peptide mutants, leading to a more precise analysis of pathogenic mutations for developing effective diagnosis and treatment. Three types of single‐point mutants of Amyloid‐β peptide associated with familial Alzheimer's disease were simultaneously identified with aerolysin nanopores assisted by a 3D blockage mapping strategy. This is based on the combination of the conventional current blockage (Ib/I0), duration time (tD) and the reliable standard deviation of current blockade fluctuations (σb).