Burnouf, S;
Gorsky, MK;
Dols, J;
Grönke, S;
Partridge, L;
(2015)
Aβ43 is neurotoxic and primes aggregation of Aβ40 in vivo.
Acta Neuropathologica
, 130
(1)
pp. 35-47.
10.1007/s00401-015-1419-y.
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Abstract
The involvement of Amyloid-β (Aβ) in the pathogenesis of Alzheimer’s disease (AD) is well established. However, it is becoming clear that the amyloid load in AD brains consists of a heterogeneous mixture of Aβ peptides, implying that a thorough understanding of their respective role and toxicity is crucial for the development of efficient treatments. Besides the well-studied Aβ and Aβ species, recent data have raised the possibility that Aβ peptides might be instrumental in AD pathogenesis, because they are frequently observed in both dense and diffuse amyloid plaques from human AD brains and are highly amyloidogenic in vitro. However, whether Aβ is toxic in vivo is currently unclear. Using Drosophila transgenic models of amyloid pathology, we show that Aβ peptides are mainly insoluble and highly toxic in vivo, leading to the progressive loss of photoreceptor neurons, altered locomotion and decreased lifespan when expressed in the adult fly nervous system. In addition, we demonstrate that Aβ species are able to trigger the aggregation of the typically soluble and non-toxic Aβ, leading to synergistic toxic effects on fly lifespan and climbing ability, further suggesting that Aβ peptides could act as a nucleating factor in AD brains. Altogether, our study demonstrates high pathogenicity of Aβ species in vivo and supports the idea that Aβ contributes to the pathological events leading to neurodegeneration in AD.
| Type: | Article |
|---|---|
| Title: | Aβ43 is neurotoxic and primes aggregation of Aβ40 in vivo |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00401-015-1419-y |
| Publisher version: | http://dx.doi.org/10.1007/s00401-015-1419-y |
| Additional information: | © The Author(s) 2015. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1468234 |
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