| BackgroundParkinson's Disease(PD)is the second most common degenerative Disease of the central nervous system in the elderly.The clinical manifestations are mainly motor symptoms,including bradykinesia,resting tremor,myotonia and posture disorder.The main pathological changes of PD are the loss of dopaminergic neurons in the substantia nigra and the appearance of Lewy bodies(LB)in the cytoplasm of the remaining neurons.The main component of LB is a-synuclein(?-syn),which is also the first protein identified to be associated with PD.At present,autopsy pathological examination is still the gold standard for the diagnosis of PD.Due to the lack of specific biomarkers,the diagnosis of PD patients mainly depends on typical motor symptoms and response to levodopa.Even experienced neurologists,the misdiagnosis rate of PD is as high as 10%to 20%.Therefore,the study of in vivo pathological biomarkers in patients with PD is very important for the early diagnosis of Parkinson's disease.Previous studies have shown that skin biopsy has higher sensitivity and specificity than other tissue biopsies to detect phosphorylated ?-syn(p-?-syn),highly suggesting that skin biopsy p-?-syn may be a more reliable peripheral biomarker of Parkinson's disease.ObjectiveTo investigate the characteristics of phosphorylated a-synuclein(p-a-syn)deposition in skin nerve fibers and it's potential as a peripheral biomarker for Parkinson's disease(PD).Methods1.Subjects Thirty-one cases of clinically confirmed PD patients and 45 healthy volunteers of the same age who were admitted to the department of neurology of the first affiliated hospital of zhengzhou university from June 1,2017 to December 31,2019 were included,and Small-Fiber Neuropathy and Symptoms Inventory Questionnaire(SFN-SIQ)were evaluated.According to the main clinical manifestations,PD patients were divided into two subgroups:bradykinesia(n=16)and resting tremor(n=15).The severity of the disease was evaluated by Hoehn Yahr grade,of which stage 0?2.5 was the early group(n=23),and the period from 3 to 5 is the middle-late group(n=8).2.skin biopsy Three-millimeter punch biopsies were taken from cervical seven paravertebral area and distal leg of PD patients,while the skin of the distal leg of healthy control group was only taken,followed by immunohistochemistry and double immunofluorescence staining.The intraepidermal nerve fiber density(IENFD)and the deposition characteristics of p-?-syn were studied.3.Statistical analysis All statistical analyses were performed using SPSS 25.0 software.Continuous variables that conformed to the normal distribution were expressed as mean ± standard deviation.Student t-test was done to determine difference among continuous variables.When the normal distribution was not satisfied,the median was used for comparison;Categorical variables were expressed in terms of counts and percentages[n(%)],using chi-square test or Fisher analysis.Spearman correlation analysis was used for the correlation between continuous variable data and between categorical and continuous variable data.All the statistics were tested by two-sided test,and P<0.05 was considered to be significant.Results1.P-?-syn immuosignals were observed in 24(77.42%)PD patients while in none of the control subjects,the distributed in shape of dots or thread in the subepithelial plexus,dermis nerve tracts,and/or in the nerve fibers innervating sweat gland,muscle arrector pilorum,small blood vessels or hair follicle.The positive rate of p-?-syn deposition in a single site was 35.48%(11/31)of the distal leg,48.39%(15/31)ofthe cervical,and the total positive rate was 77.42%(24/31).2.The IENFD of PD group was 5.75± 2.46/mm,which was significantly lower than that of control group(9.75 ± 4.32/mm,t=-4.541,P<0.001),and was negatively correlated with the SFN-SIQ(r=-0.434,P=0.019).3.There was no statistically significant difference in the positive rate of p-?-syn deposition and IENFD between patients with tremor and bradykinesia,nor between patients at early group and middle-late group.ConclusionCutaneous p-?-syn deposits in the nerve fibers of PD patients,with a significant decrease in IENFD.P-a-syn deposition in skin nerves may be an intrinsic peripheral pathological change of PD,and skin biopsy immunolabelling p-?-syn merit further study as a potential peripheral biomarker of in vivo PD diagnosis. |
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