Imperial College London
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Dr Francesco A. Aprile

Faculty of Natural Sciences, Department of Chemistry

Lecturer in Chemistry
 
 
 
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Contact

 

+44 (0)20 7594 5545f.aprile Website

 
 
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Location

 

110FMolecular Sciences Research HubWhite City Campus

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Summary

 

Publications

Citation

BibTex format

@article{De:2019:10.1038/s41467-019-09477-3,
author = {De, S and Wirthensohn, DC and Flagmeier, P and Hughes, C and Aprile, FA and Ruggeri, FS and Whiten, DR and Emin, D and Xia, Z and Varela, JA and Sormanni, P and Kundel, F and Knowles, TPJ and Dobson, CM and Bryant, C and Vendruscolo, M and Klenerman, D},
doi = {10.1038/s41467-019-09477-3},
journal = {Nature Communications},
pages = {1541--1541},
title = {Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms},
url = {http://dx.doi.org/10.1038/s41467-019-09477-3},
volume = {10},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Protein aggregation is a complex process resulting in the formation of heterogeneous mixtures of aggregate populations that are closely linked to neurodegenerative conditions, such as Alzheimer's disease. Here, we find that soluble aggregates formed at different stages of the aggregation process of amyloid beta (Aβ42) induce the disruption of lipid bilayers and an inflammatory response to different extents. Further, by using gradient ultracentrifugation assay, we show that the smaller aggregates are those most potent at inducing membrane permeability and most effectively inhibited by antibodies binding to the C-terminal region of Aβ42. By contrast, we find that the larger soluble aggregates are those most effective at causing an inflammatory response in microglia cells and more effectively inhibited by antibodies targeting the N-terminal region of Aβ42. These findings suggest that different toxic mechanisms driven by different soluble aggregated species of Aβ42 may contribute to the onset and progression of Alzheimer's disease.
AU  - De,S
AU  - Wirthensohn,DC
AU  - Flagmeier,P
AU  - Hughes,C
AU  - Aprile,FA
AU  - Ruggeri,FS
AU  - Whiten,DR
AU  - Emin,D
AU  - Xia,Z
AU  - Varela,JA
AU  - Sormanni,P
AU  - Kundel,F
AU  - Knowles,TPJ
AU  - Dobson,CM
AU  - Bryant,C
AU  - Vendruscolo,M
AU  - Klenerman,D
DO  - 10.1038/s41467-019-09477-3
EP  - 1541
PY  - 2019///
SN  - 2041-1723
SP  - 1541
TI  - Different soluble aggregates of Aβ42 can give rise to cellular toxicity through different mechanisms
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-019-09477-3
UR  - https://www.ncbi.nlm.nih.gov/pubmed/30948723
UR  - https://www.nature.com/articles/s41467-019-09477-3
UR  - http://hdl.handle.net/10044/1/85931
VL  - 10
ER  -
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