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

V. Donadio, K. Doppler, A. Incensi, A. Kuzkina, A. Janzen, G. Mayer, J. Volkmann, G. Rizzo, E. Antelmi, G. Plazzi, C. Sommer, R. Liguori, W. H. Oertel

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background and purpose: 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 the aim was to establish the intra- and inter-laboratory reproducibility of measurement of intraneural p-syn immunoreactivity in two laboratories with major expertise (Würzburg and Bologna). Methods: In total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA-P 4) and small fibre neuropathy (SFN 6) were enrolled. 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 protein gene product 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 for the discrepancy. Results: 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. Conclusions: Analysis of p-syn showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.

Original languageEnglish
Pages (from-to)1245-1251
Number of pages7
JournalEuropean Journal of Neurology
Volume26
Issue number10
DOIs
Publication statusPublished - Oct 1 2019

Fingerprint

Synucleins
Skin
Serine
REM Sleep Behavior Disorder
Multiple System Atrophy
Lewy Body Disease
Thigh
Parkinson Disease
Leg
Spine
Biopsy

Keywords

  • multiple system atrophy
  • Parkinson disease
  • REM sleep behaviour disorder
  • skin biopsy
  • α-synuclein deposits

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Abnormal α-synuclein deposits in skin nerves : intra- and inter-laboratory reproducibility. / Donadio, V.; Doppler, K.; Incensi, A.; Kuzkina, A.; Janzen, A.; Mayer, G.; Volkmann, J.; Rizzo, G.; Antelmi, E.; Plazzi, G.; Sommer, C.; Liguori, R.; Oertel, W. H.

In: European Journal of Neurology, Vol. 26, No. 10, 01.10.2019, p. 1245-1251.

Research output: Contribution to journalArticle

Donadio, V. ; Doppler, K. ; Incensi, A. ; Kuzkina, A. ; Janzen, A. ; Mayer, G. ; Volkmann, J. ; Rizzo, G. ; Antelmi, E. ; Plazzi, G. ; Sommer, C. ; Liguori, R. ; Oertel, W. H. / Abnormal α-synuclein deposits in skin nerves : intra- and inter-laboratory reproducibility. In: European Journal of Neurology. 2019 ; Vol. 26, No. 10. pp. 1245-1251.
@article{93612d7a2bd34242babbdd990e9886a2,
title = "Abnormal α-synuclein deposits in skin nerves: intra- and inter-laboratory reproducibility",
abstract = "Background and purpose: 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 the aim was to establish the intra- and inter-laboratory reproducibility of measurement of intraneural p-syn immunoreactivity in two laboratories with major expertise (W{\"u}rzburg and Bologna). Methods: In total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA-P 4) and small fibre neuropathy (SFN 6) were enrolled. 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 protein gene product 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 for the discrepancy. Results: The intra-laboratory analysis showed an excellent reproducibility both in W{\"u}rzburg (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. Conclusions: Analysis of p-syn showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.",
keywords = "multiple system atrophy, Parkinson disease, REM sleep behaviour disorder, skin biopsy, α-synuclein deposits",
author = "V. Donadio and K. Doppler and A. Incensi and A. Kuzkina and A. Janzen and G. Mayer and J. Volkmann and G. Rizzo and E. Antelmi and G. Plazzi and C. Sommer and R. Liguori and Oertel, {W. H.}",
year = "2019",
month = "10",
day = "1",
doi = "10.1111/ene.13939",
language = "English",
volume = "26",
pages = "1245--1251",
journal = "European Journal of Neurology",
issn = "1351-5101",
publisher = "Wiley-Blackwell Publishing Ltd",
number = "10",

}

TY - JOUR

T1 - Abnormal α-synuclein deposits in skin nerves

T2 - intra- and inter-laboratory reproducibility

AU - Donadio, V.

AU - Doppler, K.

AU - Incensi, A.

AU - Kuzkina, A.

AU - Janzen, A.

AU - Mayer, G.

AU - Volkmann, J.

AU - Rizzo, G.

AU - Antelmi, E.

AU - Plazzi, G.

AU - Sommer, C.

AU - Liguori, R.

AU - Oertel, W. H.

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Background and purpose: 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 the aim was to establish the intra- and inter-laboratory reproducibility of measurement of intraneural p-syn immunoreactivity in two laboratories with major expertise (Würzburg and Bologna). Methods: In total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA-P 4) and small fibre neuropathy (SFN 6) were enrolled. 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 protein gene product 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 for the discrepancy. Results: 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. Conclusions: Analysis of p-syn showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.

AB - Background and purpose: 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 the aim was to establish the intra- and inter-laboratory reproducibility of measurement of intraneural p-syn immunoreactivity in two laboratories with major expertise (Würzburg and Bologna). Methods: In total, 43 patients affected by Parkinson's disease (PD 21 patients), dementia with Lewy bodies (DLB 1), rapid eye movement sleep behaviour disorder (RBD 11), multiple system atrophy (MSA-P 4) and small fibre neuropathy (SFN 6) were enrolled. 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 protein gene product 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 for the discrepancy. Results: 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. Conclusions: Analysis of p-syn showed excellent inter- and intra-laboratory reproducibility supporting the reliability of this technique. The few ascertained discordances were important to further improve the standardization of this technique.

KW - multiple system atrophy

KW - Parkinson disease

KW - REM sleep behaviour disorder

KW - skin biopsy

KW - α-synuclein deposits

UR - http://www.scopus.com/inward/record.url?scp=85070103122&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070103122&partnerID=8YFLogxK

U2 - 10.1111/ene.13939

DO - 10.1111/ene.13939

M3 - Article

C2 - 30770596

AN - SCOPUS:85070103122

VL - 26

SP - 1245

EP - 1251

JO - European Journal of Neurology

JF - European Journal of Neurology

SN - 1351-5101

IS - 10

ER -