AUTHOR=Liu Xiaojing , Yang Jing , Yuan Yanpeng , He Qian , Gao Yuan , Jiang Chenyang , Li Lanjun , Xu Yuming 

TITLE=Optimization of the Detection Method for Phosphorylated α-Synuclein in Parkinson Disease by Skin Biopsy

JOURNAL=Frontiers in Neurology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.569446

DOI=10.3389/fneur.2020.569446

ISSN=1664-2295

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objective:</bold> This study aimed to optimize the skin biopsy method for detecting p-syn deposition in patients with PD.</p><p><bold>Methods:</bold> 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.</p><p><bold>Results:</bold> Deposition of p-syn were found in 75/90 PD patients but not in healthy controls (<italic>p</italic> &lt; 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%, <italic>p</italic> = 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%, <italic>p</italic> = 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 (<italic>p</italic> = 0.049).</p><p><bold>Conclusions:</bold> 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.</p>