Imperial College London
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DrJavierAlegre Abarrategui

Faculty of Medicine, Department of Brain Sciences

Clinical Senior Lecturer in Neuropathology
 
 
 
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Contact

 

+44 (0)20 7594 6683j.alegre

 
 
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Assistant

 

Mrs Hadeel Abdeen +44 (0)20 7594 7014

 
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Location

 

E416Burlington DanesHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Roberts:2015:brain/awv040,
author = {Roberts, RF and Wade-Martins, R and Alegre-Abarrategui, J},
doi = {brain/awv040},
journal = {Brain},
pages = {1642--1657},
title = {Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson's disease brain},
url = {http://dx.doi.org/10.1093/brain/awv040},
volume = {138},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Oligomeric forms of alpha-synuclein are emerging as key mediators of pathogenesis in Parkinson’s disease. Our understanding of the exact contribution of alpha-synuclein oligomers to disease is limited by the lack of a technique for their specific detection. We describe a novel method, the alpha-synuclein proximity ligation assay, which specifically recognizes alpha-synuclein oligomers. In a blinded study with post-mortem brain tissue from patients with Parkinson’s disease (n = 8, age range 73–92 years, four males and four females) and age- and sex-matched controls (n = 8), we show that the alpha-synuclein proximity ligation assay reveals previously unrecognized pathology in the form of extensive diffuse deposition of alpha-synuclein oligomers. These oligomers are often localized, in the absence of Lewy bodies, to neuroanatomical regions mildly affected in Parkinson’s disease. Diffuse alpha-synuclein proximity ligation assay signal is significantly more abundant in patients compared to controls in regions including the cingulate cortex (1.6-fold increase) and the reticular formation of the medulla (6.5-fold increase). In addition, the alpha-synuclein proximity ligation assay labels very early perikaryal aggregates in morphologically intact neurons that may precede the development of classical Parkinson’s disease lesions, such as pale bodies or Lewy bodies. Furthermore, the alpha-synuclein proximity ligation assay preferentially detects early-stage, loosely compacted lesions such as pale bodies in patient tissue, whereas Lewy bodies, considered heavily compacted late lesions are only very exceptionally stained. The alpha-synuclein proximity ligation assay preferentially labels alpha-synuclein oligomers produced in vitro compared to monomers and fibrils, while stained oligomers in human brain display a distinct intermediate proteinase K resistance, suggesting the detection of a conformer that is different from both physiological, presynapt
AU  - Roberts,RF
AU  - Wade-Martins,R
AU  - Alegre-Abarrategui,J
DO  - brain/awv040
EP  - 1657
PY  - 2015///
SN  - 1460-2156
SP  - 1642
TI  - Direct visualization of alpha-synuclein oligomers reveals previously undetected pathology in Parkinson's disease brain
T2  - Brain
UR  - http://dx.doi.org/10.1093/brain/awv040
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000357999300027&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/61093
VL  - 138
ER  -
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