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

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Version 2 2023-03-20, 13:13
Version 1 2023-03-16, 06:24
journal contribution
revised on 2023-03-20, 13:13 and posted on 2023-03-20, 13:13 authored by Nour K. Majbour, Ilham Y. Abdi, Mohammed Dakna, Tamara Wicke, Elisabeth Lang, Houda Y. Ali Moussa, Mercy A. Thomas, Claudia Trenkwalder, Bared Safieh‐Garabedian, Takahiko Tokuda, Brit Mollenhauer, Omar El‐Agnaf

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

Other Information

Published in: Movement Disorders
License: http://creativecommons.org/licenses/by/4.0/
See article on publisher's website: http://dx.doi.org/10.1002/mds.28611

History

Language

  • English

Publisher

Wiley

Publication Year

  • 2021

Institution affiliated with

  • Hamad Bin Khalifa University
  • Qatar Biomedical Research Institute
  • Qatar University

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