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  • 1
    In: Movement Disorders, Wiley, Vol. 36, No. 9 ( 2021-09), p. 2048-2056
    Abstract: 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
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2041249-6
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  • 2
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2021-3-3)
    Abstract: Background : The role of cerebrospinal fluid (CSF) alpha-synuclein as a potential biomarker has been challenged mainly due to variable preanalytical measures between laboratories. To evaluate the impact of the preanalytical factors contributing to such variability, the different subforms of alpha-synuclein need to be studied individually. Method : We investigated the effect of exposing CSF samples to several preanalytical sources of variability: (1) different polypropylene (PP) storage tubes; (2) use of non-ionic detergents; (3) multiple tube transfers; (4) multiple freeze-thaw cycles; and (5) delayed storage. CSF oligomeric- and total-alpha-synuclein levels were estimated using our in-house sandwich-based enzyme-linked immunosorbent assays. Results : Siliconized tubes provided the optimal preservation of CSF alpha-synuclein proteins among other tested polypropylene tubes. The use of tween-20 detergent significantly improved the recovery of oligomeric-alpha-synuclein, while multiple freeze-thaw cycles significantly lowered oligomeric-alpha-synuclein in CSF. Interestingly, oligomeric-alpha-synuclein levels remained relatively stable over multiple tube transfers and upon delayed storage. Conclusion : Our study showed for the first-time distinct impact of preanalytical factors on the different forms of CSF alpha-synuclein. These findings highlight the need for special considerations for the different forms of alpha-synuclein during CSF samples’ collection and processing.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2558898-9
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