Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease
作者机构：Laboratory of Translational NeuropharmacologyDepartment of Clinical NeuroscienceKarolinska InstitutetStockholmSweden Memory and Aging CenterUniversity of CaliforniaSan FranciscoSan FranciscoCAUSA Basic and Clinical NeuroscienceInstitute of PsychiatryPsychology and Neurosci-enceKing’s College LondonLondonUK Old Age PsychiatryInstitute of PsychiatryPsychology and NeuroscienceKing’s College LondonLondonUK.
出 版 物：《Translational Neurodegeneration》 (转化神经变性病（英文）)
年 卷 期：2023年第12卷第1期
页 面：315-328页
核心收录：
学科分类：1002[医学-临床医学] 100204[医学-神经病学] 10[医学]
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
主 题：Atypical Parkinsonian disorders Biomarker Cerebrospinal fluid Corticobasal syndrome DOPA decarboxylase Midkine Multiple system atrophy Parkinson’s disease Progressive supranuclear palsy Proximity extension assay
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 *** 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 *** cohorts were used in this study,comprising 192,88 and 36 cases,*** samples were run on the Cardiovascular II,Oncology II and Metabolism PEA *** Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts,respectively,compared to *** them,6 proteins were changed in both ***(MK)was increased in PD with the strongest effect size and results were validated with *** 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 ***,Kallikrein 10 was specifically changed in APD compared with both PD and controls,but unchanged between PD and *** inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent *** 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.
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