Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease  

作　　者：Wojciech Paslawski Shervin Khosousi Ellen Hertz Ioanna Markaki Adam Boxer Per Svenningsson 

机构地区：[1]Laboratory of Translational Neuropharmacology,Department of Clinical Neuroscience,Karolinska Institutet,Stockholm,Sweden [2]Memory and Aging Center,University of California,San Francisco,San Francisco,CA,USA [3]Basic and Clinical Neuroscience,Institute of Psychiatry,Psychology and Neurosci-ence,King’s College London,London,UK [4]Old Age Psychiatry,Institute of Psychiatry,Psychology and Neuroscience,King’s College London,London,UK.

出　　处：《Translational Neurodegeneration》2023年第1期315-328,共14页转化神经变性病（英文）

基　　金：Open access funding provided by Karolinska Institute;supported by Karin and Sten Mörtstedt CBD Solutions AB,the Swedish Parkinson fund,the ALF program of the Stockholm Stockholm City,Lexa/Nordstjernan,Knut and Alice Wallenberg Foundation,and Van Geest Foundation.PS is a Wallenberg Clinical Scholar.

摘　　要：Background There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease(PD).Cerebrospinal fluid(CSF)has been a successful biofluid for finding neurodegenerative biomarkers,and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies.Using a large-scale multiplex proximity extension assay(PEA)approach,we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders(APD).Methods CSF from patients with PD,corticobasal syndrome(CBS),progressive supranuclear palsy(PSP),multiple system atrophy and controls,were analysed with Olink PEA panels.Three cohorts were used in this study,comprising 192,88 and 36 cases,respectively.All samples were run on the Cardiovascular II,Oncology II and Metabolism PEA panels.Results Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts,respectively,compared to controls.Among them,6 proteins were changed in both cohorts.Midkine(MK)was increased in PD with the strongest effect size and results were validated with ELISA.Another most increased protein in PD,DOPA decarboxylase(DDC),which catalyses the decarboxylation of DOPA(L-3,4-dihydroxyphenylalanine)to dopamine,was strongly correlated with dopaminergic treatment.Moreover,Kallikrein 10 was specifically changed in APD compared with both PD and controls,but unchanged between PD and controls.Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts.Conclusions Using the large-scale PEA approach,we have identified potential novel PD diagnostic biomarkers,most notably MK and DDC,in the CSF of PD patients.

关 键 词：Atypical Parkinsonian disorders Biomarker Cerebrospinal fluid Corticobasal syndrome DOPA decarboxylase MIDKINE Multiple system atrophy Parkinson’s disease Progressive supranuclear palsy Proximity extension assay 

分 类 号：R742.5[医药卫生—神经病学与精神病学]