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CSF total and oligomeric α-Synuclein along with TNF-α as risk biomarkers for Parkinson’s disease: a study in LRRk2 mutation carriers

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Translational Neurodegeneration 2020年第2期9卷 168-177页

作者： nour k.majbour Jan O.Aasly Eldbjørg Hustad Mercy A.Thomas Nishant N.Vaikath Naser Elkum Wilma D.Jvan de Berg Takahiko Tokuda Brit Mollenhauer Henk W.Berendse Omar M.A.El-Agnaf Neurological Disorders Research Center Qatar Biomedical Research InstituteHamad Bin Khalifa UniversityQatar FoundationP.O.Box 5825DohaQatar Department of Neuroscience Norwegian University of Science and Technology(NTNU)TrondheimNorway Department of Neurology St.Olav’s HospitalUniversity Hospital of TrondheimTrondheimNorway Clinical Epidemiology Sidra Medical and Research CenterDohaQatar Department of Anatomy and Neurosciences Neuroscience Campus AmsterdamVU University Medical CentreAmsterdamthe Netherlands Department of Neurology Research Institute for GeriatricsKyoto Prefectural University of MedicineKyoto602-0841Japan Paracelsus-Elena-klinik KlinikstraßeKasseland University Medical Center GöttingenDepartment of NeurologyGöttingenGermany Department of Neurology Amsterdam UMClocation VU University Medical CentreAmsterdamThe Netherlands

Background Asymptomatic carriers of leucine-rich repeat kinase 2(LRRk2)gene mutations constitute an ideal population for discovering prodromal biomarkers of Parkinson’s disease(PD).In this study,we aim to identify CSF candidate risk biomarkers of PD in individuals with LRRk2 mutation *** We measured the levels of CSF total-(t-),oligomeric(o-)and phosphorylated S129(pS129-)α-syn,total-tau(tTau),phosphorylated threonine 181 tau(pTau),amyloid-beta 40(Aβ-40),amyloid-beta-42(Aβ-42)and 40 inflammatory chemokines in symptomatic(n=23)and asymptomatic(n=51)LRRk2 mutation carriers,subjects with a clinical diagnosis of PD(n=60)and age-matched healthy controls(n=34).General linear models corrected for age and gender were performed to assess differences in CSF biomarkers between the *** that varied significantly between the groups were then analyzed using backward-elimination logistic regression analysis to identify an ideal biomarkers panel of prodromal *** Discriminant function analysis revealed low levels of CSF t-α-syn,high levels of CSF o-α-syn and TNF-αbest discriminated asymptomatic LRRk2 mutation carriers from both symptomatic PD and healthy *** the discriminative power using receiver operating curve analysis,an area under the curve>0.80 was *** The current study suggests that CSF t-,o-α-syn and TNF-αare candidate risk biomarkers for the detection of PD at the prodromal *** findings also highlight the dynamic interrelationships between CSF proteins and the importance of using a biomarkers’panel approach for an accurate and timely diagnosis of PD.

关键词： Parkinson's disease LRRk2 mutation carriers Alpha-synuclein oligomers Biomarkers Inflammatory markers

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