The elucidation of Abeta aggregation mechanism using high-speed atomic force microscopy

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461266
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Showa University (2015-2016); Kanazawa University (2014)
• Principal Investigator: Ono Kenjiro 昭和大学, 医学部, 教授 (70377381)
• Co-Investigator(Renkei-kenkyūsha): YAMADA Masahito 金沢大学, 医学系, 教授 (80191336) ; NAKAYAMA Takahiro 金沢大学, バイオAFM先端研究センター, 助教 (00532821)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: アルツハイマー病 / アミロイドβ蛋白 / 高速原子間力顕微鏡

Outline of Final Research Achievements

Aggregation of amyloid β-protein (Aβ) into insoluble amyloid fibrils is implicated in Alzheimer's disease (AD). The elucidation of the structural features and assembly kinetics of Aβ has been an area of intense study. We performed high-speed atomic force microscopy (HS-AFM) studies of fibril formation and elongation by Aβ1-42. Our data demonstrate two different growth modes of Aβ1-42, one producing straight fibrils and the other producing spiral fibrils. Each mode depends on initial fibril nucleus structure, but switching from one growth mode to another was occasionally observed, suggesting that fibril end structure fluctuated between the two growth modes. This switching phenomenon was affected by buffer salt composition. Our findings indicate that polymorphism in fibril structure can occur after fibril nucleation and is affected by relatively modest changes in environmental conditions.

Free Research Field

神経内科学、神経化学