AI Article Synopsis
- Aβ42 oligomers are highly toxic to neurons and can enter them, leading to neurodegeneration in Alzheimer’s disease.
- In contrast, Aβ42 fibrils are less toxic and don’t enter neurons as effectively, despite sonication making them similar in size to oligomers.
- Prolonged exposure (24 hours) to Aβ42 oligomers can trigger lasting neurotoxicity in cells.
Article Abstract
Amyloid fibrils found in plaques in Alzheimer's disease (AD) brains are composed of amyloid-β peptides. Oligomeric amyloid-β 1-42 (Aβ42) is thought to play a critical role in neurodegeneration in AD. Here, we determine how size and conformation affect neurotoxicity and internalisation of Aβ42 assemblies using biophysical methods, immunoblotting, toxicity assays and live-cell imaging. We report significant cytotoxicity of Aβ42 oligomers and their internalisation into neurons. In contrast, Aβ42 fibrils show reduced internalisation and no toxicity. Sonicating Aβ42 fibrils generates species similar in size to oligomers but remains nontoxic. The results suggest that Aβ42 oligomers have unique properties that underlie their neurotoxic potential. Furthermore, we show that incubating cells with Aβ42 oligomers for 24 h is sufficient to trigger irreversible neurotoxicity.
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| http://dx.doi.org/10.1002/1873-3468.13919 | DOI Listing |
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