Nour K Majbour1, Ilham Y Abdi1,2, Mohammed Dakna3, Tamara Wicke4, Elisabeth Lang4, Houda Y Ali Moussa1, Mercy A Thomas1, Claudia Trenkwalder4,5, Bared Safieh-Garabedian6, Takahiko Tokuda7, Brit Mollenhauer3,4, Omar El-Agnaf1. 1. Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Doha, Qatar. 2. College of Health and Life Sciences, Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar. 3. Department of Neurology, University Medical Center Goettingen, Goettingen, Germany. 4. Paracelsus-Elena-Klinik, Kassel, Germany. 5. Department of Neurosurgery, University Medical Center Goettingen, Goettingen, Germany. 6. Member of QU Health, College of Medicine, Qatar University, Doha, Qatar. 7. Department of Neurology, Research Institute for Geriatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Abstract
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.
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 PDpatients 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.
Authors: Lara Blömeke; Marlene Pils; Victoria Kraemer-Schulien; Alexandra Dybala; Anja Schaffrath; Andreas Kulawik; Fabian Rehn; Anneliese Cousin; Volker Nischwitz; Johannes Willbold; Rebecca Zack; Thomas F Tropea; Tuyen Bujnicki; Gültekin Tamgüney; Daniel Weintraub; David Irwin; Murray Grossman; David A Wolk; John Q Trojanowski; Oliver Bannach; Alice Chen-Plotkin; Dieter Willbold Journal: NPJ Parkinsons Dis Date: 2022-06-02