Internalisation and toxicity of amyloid-β 1-42 are influenced by its conformation and assembly state rather than size

FEBS Letters

article

Devkee M. Vadukul¹  Mahmoud Maina¹  Hannah Franklin¹  Astrid Nardecchia¹  Louise C. Serpell¹  Karen E. Marshall¹ 

[1] Dementia Research group, School of Life Sciences, University of Sussex;Institute of Neuroscience, Université catholique de Louvain;College of Medical Sciences, Yobe State University

关键词: Alzheimer’s disease;    amyloid fibril;    neurotoxicity;    oligomer;   

DOI  :  10.1002/1873-3468.13919

来源: John Wiley & Sons Ltd.

【 摘 要 】

Amyloid fibrils found in plaques in Alzheimer’s disease (AD) brains are composed of amyloid-b peptides. Oligomeric amyloid-b 1-42 (Ab42) is thought to play a critical role in neurodegeneration in AD. Here, we determine how size and conformation affect neurotoxicity and internalisation of Ab42 assemblies using biophysical methods, immunoblotting, toxicity assays and live-cell imaging. We report significant cytotoxicity of Ab42 oligomers and their internalisation into neurons. In contrast, Ab42 fibrils show reduced internalisation and no toxicity. Sonicating Ab42 fibrils generates species similar in size to oligomers but remains nontoxic. The results suggest that Ab42 oligomers have unique properties that underlie their neurotoxic potential. Furthermore, we show that incubating cells with Ab42 oligomers for 24 h is sufficient to trigger irreversible neurotoxicity.

【 授权许可】

Unknown