Serum Metabolomics Study Of The Development Of Parkinson’s Disease

ObjectiveParkinson’s disease(PD),also known as tremor paralysis,was compared in serum metabolomics between Parkinson’s disease and healthy control groups,as well as between different subtypes of Parkinson’s disease.Differential metabolites were identified and enriched for analysis to explore diagnostic biomarkers of Parkinson’s disease,providing useful information for the diagnosis and treatment of Parkinson’s disease.Methods1.In this research,179 patients with Parkinson’s disease(PD),including 90 males and 8 9 females,were collected from the neurology department of our hospital.1 0 1patients,including 55 males and 46 females,were selected as the control group.The selected subjects’ serum was detected by high performance liquid chromatography-mass spectrometry.2.Clinical data were collected from the PD group: name,gender,age,past history(e.g.hypertension,hyperlipidemia,cranial trauma,medication history),smoking history,alcohol history,family history,onset of motor symptoms,non-motor symptoms,Hoehh&Yahr scale,Mini-mental State Examination(MMSE),and the Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Pittsburgh sleep quality index(PSQI),Movement Disorders Society-The MDS-UPDRS,etc.Basic information was collected from healthy controls: name,gender and age.3.Statistical analysis of routine data: SPSS 26.0 was used for data analysis.Measures conforming to a normal distribution were expressed as X±SD,and those not conforming to a normal distribution were expressed as median with interquartile spacing.Comparisons between two groups were made by t-test(conforming to normal distribution with chi-square),or Wilcoxon rank sum test(skewed distribution or chi-square);count data were expressed as frequencies and analysed using chi-square test or Fisher’s exact probability method.p < 0.05 was considered to be statistically significant.4.Metabolomics data analysis: Univariate and multivariate statistical analyses of normalized data were performed using Metabo Analyst 5.0 for pattern recognition,and metabolites were selected between groups according to the following principles:(1)adjusted Pvalue < 0.05;(2)fold-change of significant difference in expression(> 1.2 or < 0.9).enriched pathway analysis was performed using the platform as above.Results1.72 differential serum metabolites were identified in patients with Parkinson’s disease compared with healthy controls,of which 41 metabolites were upregulated and 31 metabolites were down regulated,and the differences were statistically significant(P < 0.05);2.A total of 74 differential metabolites were identified in postural instability/gait disturbance type(PIGD type)PD compared to healthy controls;43 metabolites were upregulated including triethanolamine,trans-2-hexenoicacid,triiodothyronine glucosinolate,delta-methyl viologenone,isoleucoyl proline,and31 metabolites were downregulated including budesine,2-oxoarginine,Nacetylarylamine,xi-p-menthane-1(7),2-diene-4-alcohol,3-isohumulone.3.A total of 135 differential metabolites were identified intremor-dominant(TD)PD compared with healthy controls,with 76 metabolites up-regulated,including 2-biphenyllen-10-ol,tetrahydro-5-isopropenyl-2-methyl-2-vinylfuran,Armillarin,ethanoic acid phosphate,2-methylfuran,and 59 metabolites downregulated,,including uric acid,norvaline,2-piperidone,etapivirine and diisobutyl phthalate.4.A total of 58 differential metabolites were identified in mixed(IT-type)PD compared to healthy controls,with 31 metabolites up-regulated,including triethanolamine,trans-2-hexenoic acid,(-)-trans-pineol,selenium phosphite,and Pulegone,and 27 metabolites down-regulated,including ethyl crotonate,photocitral A,gamma-caprolactone,carviol,and etanercept.5.A total of 32 differential metabolites were screened between the different motor subtypes of PD,including etapressin,carviolol,2-piperidone,gammacaprolactone,and isopentenyl formate;6.Compared with early PD,9 metabo lites such as dehydrolinalool and β-leucine were up-regulated in middle PD,while 2,4-pentadienal and 5-oxy-2(5H)-isooxazolpropyl nitrile were down-regul ated in total.Eight metabolites,including β-leucine and cis-citral,were down-regulated in late PD compared with middle PD.7.24 differential metabolites were identified in the early-onset PD group compared to the late-onset PD group.17 metabolites,including diisobutyl phthalate,L-allo-isoleucine,Phosphohydroxypyruvic acid,,weredown-regulated,and 2’-aminoacetophenone,3-methylcyclopentene,δ-hexanoicacid lactone,and seven other metabolites were upregulated;8.There were 8 different metabolic pathway s between PD patients and healthy controls,among which histidine metabolism,arginine biosynthesis and D-arginine/D-ornithine metabolism showed the greatest difference between PD patients and healthy controls.The metabolic pathways of PD with different exercise subtypes are D-arginine/D-ornithine and glycine/serine/threonine.The differential metabolic pathways of early-onset PD and late-onset PD are glycine/serine/threonine and cysteine/methionine.ConclusionsThere is a clear distinction in serum metabolomics between Parkinson’s disease and healthy groups,as well as between subgroups of Parkinson’s disease.The differences in metabolites suggest changes in amino acid metabolism,lipids,and metabolic pathways in Parkinson’s disease,which have certain reference value for the diagnosis of Parkinson’s disease.