Vadukul-early-FEBS.pdf (1.64 MB)
Internalisation and toxicity of amyloid-ß 1-42 are influenced by its conformation and assembly state rather than size
journal contribution
posted on 2023-06-10, 00:59 authored by Devkee M Vadukul, Mahmoud MainaMahmoud Maina, Hannah Franklin, Astrid Nardecchia, Louise SerpellLouise Serpell, Karen MarshallKaren MarshallAmyloid fibrils found in plaques in Alzheimer’s disease (AD) brains are composed of amyloid-ß peptides. Oligomeric amyloid-ß 1-42 (Aß42) is thought to play a critical role in neurodegeneration in AD. Here, we determine how size and conformation affect neurotoxicity and internalisation of Aß42 assemblies using biophysical methods, immunoblotting, toxicity assays and live-cell imaging. We report significant cytotoxicity of Aß42 oligomers and their internalisation into neurons. In contrast, Aß42 fibrils show reduced internalisation and no toxicity. Sonicating Aß42 fibrils generates species similar in size to oligomers but remains nontoxic. The results suggest that Aß42 oligomers have unique properties that underlie their neurotoxic potential. Furthermore, we show that incubating cells with Aß42 oligomers for 24 h is sufficient to trigger irreversible neurotoxicity.
History
Publication status
- Published
File Version
- Published version
Journal
FEBS LettersISSN
0014-5793Publisher
ElsevierExternal DOI
Issue
21Volume
594Page range
3490-3503Event location
EnglandDepartment affiliated with
- Biochemistry Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-09-17First Open Access (FOA) Date
2021-09-17First Compliant Deposit (FCD) Date
2021-09-15Usage metrics
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