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 language | English |
|---|---|
| Pages (from-to) | 1245-1251 |
| Number of pages | 7 |
| Journal | European Journal of Neurology |
| Volume | 26 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - Oct 1 2019 |
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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 journal › Article
}
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 -