Cerebrospinal α-Synuclein Oligomers Reflect Disease Motor Severity in DeNoPa Longitudinal Cohort.

Autor: Majbour NK; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar., Abdi IY; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar.; College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar., Dakna M; Department of Neurology, University Medical Center Goettingen, Goettingen, Germany., Wicke T; Paracelsus-Elena-Klinik, Kassel, Germany., Lang E; Paracelsus-Elena-Klinik, Kassel, Germany., Ali Moussa HY; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar., Thomas MA; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar., Trenkwalder C; Paracelsus-Elena-Klinik, Kassel, Germany.; Department of Neurosurgery, University Medical Center Goettingen, Goettingen, Germany., Safieh-Garabedian B; Member of QU Health, College of Medicine, Qatar University, Doha, Qatar., Tokuda T; Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan., Mollenhauer B; Department of Neurology, University Medical Center Goettingen, Goettingen, Germany.; Paracelsus-Elena-Klinik, Kassel, Germany., El-Agnaf O; Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar.
Jazyk: angličtina
Zdroj: Movement disorders : official journal of the Movement Disorder Society [Mov Disord] 2021 Sep; Vol. 36 (9), pp. 2048-2056. Date of Electronic Publication: 2021 May 12.
DOI: 10.1002/mds.28611
Abstrakt: Background: Tangible efforts have been made to identify biomarkers for Parkinson's disease (PD) diagnosis and progression, with α-synuclein (α-syn) related biomarkers being at the forefront.
Objectives: The objectives of this study were to explore whether cerebrospinal fluid (CSF) levels of total, oligomeric, phosphorylated Ser 129 α-synuclein, along with total tau, phosphorylated tau 181, and β-amyloid 1-42 are (1) informative as diagnostic markers for PD, (2) changed over disease progression, and/or (3) correlated with motor and cognitive indices of disease progression in the longitudinal De Novo Parkinson cohort.
Methods: A total of 94 de novo PD patients and 52 controls at baseline and 24- and 48-month follow-up were included, all of whom had longitudinal lumbar punctures and clinical assessments for both cognitive and motor functions. Using our in-house enzymelinked immunosorbent assays and commercially available assays, different forms of α-synuclein, tau, and β-amyloid 1-42 were quantified in CSF samples from the De Novo Parkinson cohort.
Results: Baseline CSF total α-synuclein was significantly lower in early de novo PD compared with healthy controls, whereas the ratio of oligomeric/total and phosphorylated/total were significantly higher in the PD group. CSF oligomeric-α-synuclein longitudinally increased over the 4-year follow-up in the PD group and correlated with PD motor progression. Patients at advanced stages of PD presented with elevated CSF oligomeric-α-synuclein levels compared with healthy controls.
Conclusions: Longitudinal transitions of CSF biomarkers over disease progression might not occur linearly and are susceptible to disease state. CSF oligomeric-α-synuclein levels appear to increase with diseases severity and reflect PD motor rather than cognitive trajectories. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
(© 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)
Databáze: MEDLINE
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