Case-control Study Explores Peripheral Blood Biomarkers For Diagnosis Of Parkinson’s Disease

Background and ObjectiveAccurate diagnosis of Parkinson’s disease(PD)is challenging,especially at early stages,due to clinical overlap with Parkinson-plus syndrome(PPS)such as progressive supranuclear palsy(PSP)and multiple system atrophy(MSA).To date,a biomarker for PD detection remains an unmet need,despite promises of potential biomarkers such as α-synuclein(α-Syn)in cerebrospinal fluid(CSF).Specific PD genes,such as SNCA,glucocerebrosidase(GBA),leucine rich repeat kinase 2(LRRK2)and synaptojanin 1(SYNJ1),can be useful to diagnose or assess the risk of familial PD but very few genes including those related to inherited PD are useful to detect sporadic PD.Gene chip technology has increasingly been used to explore the genetic architecture of PD.However,due to the disparities in quality,small sample sizes and sample population differences of each study,single-chip assays cannot adequately reflect the full genetic profiles of PD.In the early stage,our research group used meta-analysis statistical methods to integrate the data of different research groups,and found the four key genes of Parkinson’s disease,PPP2CA,PPP3CB,SYNJ1,and NSF.Now we plan to further clinically verify,detect these four genes expression level in Parkinson’s disease(PD),Parkinson-plus syndrome(PPS)and healthy controls(HC),explore the sensitivity and specificity of PPP2CA,PPP3CB,SYNJ1,NSF genes in the diagnosis of Parkinson’s disease,and find an effective peripheral blood biomarker to diagnose the Parkinson’s disease.MethodWe enrolled patients with PD or PPS from 27 December 2018 to 20 October 2019 from four medical centers:Zhujiang Hospital of Southern Medical University,the First People’s Hospital of Guangzhou,the Guangdong Second Provincial General Hospital and the Fifth Affiliated Hospital of Southern Medical University.Additionally,we recruited HC subjects from the Medical Examination Center of Zhujiang Hospital of Southern Medical University at the same time.We collected data on the baseline information and three milliliters of venous blood sample from every participant.Psychiatric dysfunction,activities of daily life(ADLs)and motor disorders were measured by the Unified Parkinson’s Disease Rating Scale(UPDRS)Ⅰ-Ⅳ.The stage of the parkinson disease was measured by the modified Hoehn and Yahr Staging Scale(H&Y).Real-time PCR(qPCR)was carried out to determine the expression levels of PP2CA,PPP3CB,SYNJ1 and NSF genes.ResultA total of 238 subjects were enrolled in this study,including 90 PD patients,23 PPS patients and 125 healthy controls.The results of all data are as follows:1.Among three groups,the peripheral blood levels of PPP2CA,SYNJ1 and NSF in PD were significantly lower than those in HC subjects,respectively;the blood level of SYNJ1 was significantly decreased in PD patients compared to PPS subjects;there was no difference of PPP3CB among three groups.2.ROC analysis was conducted to verify whether these genes could differentiate PD from HC and PPS subjects.In discriminating PD patients from HCs,AUCs for PPP2CA,SYNJ1,NSF and the combination of these three genes were measure,the AUC for the combination was higher than that of other genes,but the same as the AUC for SYNJ1.Moreover,for discriminating PD from PPS,the AUC of SYNJ1 was 0.874,with 82.61%sensitivity and 91.11%specificity.The AUC of SYNJ1 is similar with combination but higher than other genes.3.Multinomial Logistic Regression Analysis showed PPP2CA and SYNJ1 as independent risk factors of PD compared with HC and PPS.4.The levels of PPP2CA,PPP3CB,SYNJ1 and NSF were negatively correlated with UPDRS Ⅱ-Ⅲ and total UPDRS scores and H&Y scales.Conclusion1.SYNJ1 may be a potential peripheral biomarker to discriminate PD from HC and PPS.2.PPP2CA、SYNJ1 and NSF.may be a potential peripheral biomarker to discriminate PD from HC.3.The expression levels of peripheral PPP2CA,PPP3CB,SYNJ1 and NSF genes in patients with Parkinson’s disease are negatively correlated with the severity of disease.