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

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