Abstract
Background: Recent studies have found deposition of phosphorylated α-synuclein (p-syn) in Parkinson disease (PD) patients' skin, indicating p-syn may be a potential biomarker of PD. However, the sensitivity of the p-syn detection varied largely from 5. 3 to 100%, this influenced the clinical use of this detection method to some extent.Objective: This study aimed to optimize the skin biopsy method for detecting p-syn deposition in patients with PD.Methods: Ninety PD patients and 30 healthy controls underwent skin biopsies at 2–3 of the following sites: the distal leg, thigh, cervical region, or forearm. Skin biopsy samples were cut to 50- and 15-μm thickness sections. Deposition of p-syn were detected by using double immunofluorescence labeling of protein gene production 9.5 (PGP9.5) /p-syn. Statistical data analysis was performed using SPSS 25.0 software.Results: Deposition of p-syn were found in 75/90 PD patients but not in healthy controls (p < 0.001). The positive deposition rate of p-syn in the single cervical site was significantly higher than that in the distal leg, thigh, and forearm site. Two samples from the cervical region had a higher p-syn positive rate compared to single cervical site (90.5 vs. 66.7%, p = 0.037). There was no significant difference between the p-syn positive rate of samples from the distal leg/cervical sites and 2 samples from cervical region (80 vs. 90.5%, p = 0.261). Next, the p-syn positive deposition rate of 2-biopsy samples including distal leg/cervical sites and double samples in the cervical site were comparable to the 3-biopsy samples. The 50-μm section had a significantly higher p-syn positive rate than the 15-μm section (p = 0.049).Conclusions: Two biopsy sites (cervical/distal leg) or 2 samples from the cervical site were considered to be priority biopsy sites for detecting p-syn in PD patients. Thick sections may provide a higher p-syn positive rate than thin sections for skin biopsies. These findings provide an optimized p-syn detection method, indicate the valuable pathology biomarker of PD and will promote the clinical use of skin biopsy in the future.
Highlights
Parkinson disease (PD) is one of the most common neurodegenerative movement disorders [1]
We found that the positive rate of p-syn deposits in the skin of PD patients varies from 5.3 to 100% due to the use of different biopsy sites, number of samples, and thickness of sections [5, 9, 13], which affects the diagnostic efficiency in PD, and the clinical application of skin biopsy
Our study aims to optimize the method for detecting p-syn in the skin of PD patients by comparing the p-syn positive rate of different biopsy sites, the number of samples biopsied, and the thickness of sections
Summary
Parkinson disease (PD) is one of the most common neurodegenerative movement disorders [1]. P-syn was found in synucleinopathies, such as PD, Lewy bodies (DLB), and multiple system atrophy (MSA), but not in normal controls and taupathies [7,8,9,10,11,12]. These evidences indicated cutaneous p-syn could be a reliable peripheral biomarker for PD diagnosis. Recent studies have found deposition of phosphorylated α-synuclein (p-syn) in Parkinson disease (PD) patients’ skin, indicating p-syn may be a potential biomarker of PD. The sensitivity of the p-syn detection varied largely from 5. 3 to 100%, this influenced the clinical use of this detection method to some extent
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