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Eur J Neurol. 2019 Feb 15. doi: 10.1111/ene.13939. [Epub ahead of print]

Abnormal α-synuclein deposits in skin nerves: intra- and inter-laboratory reproducibility.

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IRCCS Institute of Neurological Sciences, Bologna, Italy.
Department of Neurology, University Hospital Würzburg, Würzburg, Germany.
Philipps University, Marburg, Germany.



Visualization of phosphorylated α-synuclein at serine 129 (p-syn) in skin nerves is a promising test for the in vivo diagnosis of synucleinopathies. Here we aimed to establish the intra- and inter-laboratory reproducibility of quantification of intraneural p-syn immunoreactivity in two laboratories with a major expertise (Würzburg and Bologna).


We enrolled 43 patients affected by Parkinson's disease (PD: 21 patients), Dementia with Lewy Body (DLB: 1), REM sleep behavior disorder (RBD: 11), Multiple System Atrophy (MSA-P: 4) and small fiber neuropathy (SFN: 6). Skin biopsy was performed at the C7 paravertebral spine region and distal skin sites (thigh or leg). The analysis was standardized in both laboratories and carried out blinded on a single skin section double stained with antibodies to p-syn and the pan-axonal marker PGP 9.5. Fifty skin sections were randomly selected for the analysis: 25 from C7 and 25 from distal sites. Differently classified sections were re-evaluated to understand the reasons of the discrepancy.


The intra-laboratory analysis showed an excellent reproducibility both in Würzburg (concordance of classification 100% of sections; K=1; p<0.001) and Bologna (96% of sections; K=0.92; p<0.001). Inter-laboratory analysis showed reproducibility in 45 sections (90%; K=0.8; p<0.001) and a different classification in five sections, which was mainly due to fragmented skin samples or weak fluorescent signals.


1) p-syn analysis showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique as in vivo biomarker for synucleinopathies; 2) the few ascertained discordances were important to further improve the standardization of this technique. This article is protected by copyright. All rights reserved.


MSA ; RBD ; Parkinson disease; skin biopsy; α-synuclein deposits


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