Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

Chelpin, Marianne von Euler; Söderberg, Linda; Fälting, Johanna; Möller, Christer; Giorgetti, Marco; Constantinescu, Radu; Blennow, Kaj; Zetterberg, Henrik; Höglund, Kina

doi:10.3233/jpd-202141

Cited by 6 publications

(4 citation statements)

References 52 publications

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“…A recent study employed single-molecule array (Simoa), an ultra-sensitive technology, to quantitate very low concentrations (picomolar to femtomolar) of α-synuclein protofibrils (PFs) in CSF of PD patients and observed an increased concentration of α-synuclein PFs in PD patients (von Euler Chelpin et al, 2020).…”

Section: α-Synuclein In Cerebrospinal Fluid (Csf)mentioning

confidence: 99%

“…The measurement of CSF α-synuclein in combination with FMS-like tyrosine kinase 3 ligand (FLT3L) or the percentage phosphorylated tau (p-tau) clearly distinguished PD from MSA in a study ( Shi et al, 2011 ). A recent study employed single-molecule array (Simoa), an ultra-sensitive technology, to quantitate very low concentrations (picomolar to femtomolar) of α-synuclein protofibrils (PFs) in CSF of PD patients and observed an increased concentration of α-synuclein PFs in PD patients ( von Euler Chelpin et al, 2020 ). The increased baseline level of misfolded α-synuclein aggregate in CSF (measured by protein misfolding cyclic amplification technique) has been reported in a follow-up study as a risk factor for the development of dementia in PD ( Ning et al, 2019 ).…”

Section: α-Synuclein As a Biomarkermentioning

confidence: 99%

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Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Ganguly

Singh

Pal

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the second most common neurodegenerative disorder of the elderly, presenting primarily with symptoms of motor impairment. The disease is diagnosed most commonly by clinical examination with a great degree of accuracy in specialized centers. However, in some cases, non-classical presentations occur when it may be difficult to distinguish the disease from other types of degenerative or non-degenerative movement disorders with overlapping symptoms. The diagnostic difficulty may also arise in patients at the early stage of PD. Thus, a biomarker could help clinicians circumvent such problems and help them monitor the improvement in disease pathology during anti-parkinsonian drug trials. This review first provides a brief overview of PD, emphasizing, in the process, the important role of α-synuclein in the pathogenesis of the disease. Various attempts made by the researchers to develop imaging, genetic, and various biochemical biomarkers for PD are then briefly reviewed to point out the absence of a definitive biomarker for this disorder. In view of the overwhelming importance of α-synuclein in the pathogenesis, a detailed analysis is then made of various studies to establish the biomarker potential of this protein in PD; these studies measured total α-synuclein, oligomeric, and post-translationally modified forms of α-synuclein in cerebrospinal fluid, blood (plasma, serum, erythrocytes, and circulating neuron-specific extracellular vesicles) and saliva in combination with certain other proteins. Multiple studies also examined the accumulation of α-synuclein in various forms in PD in the neural elements in the gut, submandibular glands, skin, and the retina. The measurements of the levels of certain forms of α-synuclein in some of these body fluids or their components or peripheral tissues hold a significant promise in establishing α-synuclein as a definitive biomarker for PD. However, many methodological issues related to detection and quantification of α-synuclein have to be resolved, and larger cross-sectional and follow-up studies with controls and patients of PD, parkinsonian disorders, and non-parkinsonian movement disorders are to be undertaken.

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Section: α-Synuclein In Cerebrospinal Fluid (Csf)mentioning

confidence: 99%

Section: α-Synuclein As a Biomarkermentioning

confidence: 99%

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Ganguly

Singh

Pal

et al. 2021

Front. Aging Neurosci.

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“…An enzyme-linked immunosorbent assay (ELISA) kit (catalog number: 844101, Legend Max, BioLegend, USA) was employed to measure total α-syn levels in CSF samples. Oligo-alpha-synuclein (oligo-aSyn) concentration was measured using an in-house Single molecule array (Simoa) assay employing an oligo-aSyn-selective capture antibody, as previously described [21].…”

Section: Cerebrospinal Uidmentioning

confidence: 99%

Neuroinflammation In Parkinson’s Disease: A Study With [11C]PBR28 PET And Cerebrospinal Fluid Markers

Al-Abdulrasul

Ajalin

Tuisku

et al. 2022

Preprint

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Purpose To investigate neuroinflammation in Parkinson’s disease (PD) with [11C]PBR28 positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers, and the relationship to dopaminergic functioning measured with 6-[18F]-fluoro-L-dopa ([18F]FDOPA) PET. Methods The clinical cohort consisted of 20 patients with PD and 51 healthy controls (HC). All HC and 15 PD participants underwent [11C]PBR28 High Resolution Research Tomograph (HRRT) PET examination for the quantitative assessment of cerebral binding to the translocator protein (TSPO), a neuroinflammation marker. CSF samples were available from 17 patients with PD and 21 HC and were examined for soluble triggering receptor expressed on myeloid cells 2 (sTREM2), chitinase 3-like 1 protein (YKL-40), neurogranin (NG), alpha-synuclein (aSyn) and oligo-alpha-synuclein. All patients with PD underwent [18F]FDOPA HRRT PET examination. Results Subjects with PD and HC did not differ in the total volume of distribution (VT) of [11C]PBR28 in any studied brain regions. In the CSF analyses, higher levels of sTREM2 and NG were associated with more severe motor symptoms evaluated by The Unified Parkinson’s Disease Rating Scale motor part (UPDRS-III) (p = 0.041 and p = 0.016 respectively). Additionally, in the PD group increased VT in the basal ganglia and substantia nigra (SN) were related to higher levels of YKL-40 (p < 0.01). No significant correlations were found between [11C]PBR28 VT and [18F]FDOPA uptake or between [11C]PBR28 VT and UPDRS-III in any studied region. No significant correlations were observed between the CSF markers and [18F]FDOPA uptake in the SN or the striatum. No significant correlations were found between [11C]PBR28 VT and aSyn, oligo-aSyn or their ratio. Conclusion Associations between CSF biomarkers, motor disability and [11C]PBR28 VT in the striatum and SN may support a role for neuroinflammation in PD.

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“…A problem with diagnosing PD is a major challenge because there is no definitive biomarker for early diagnosis resulting in difficulty of better management of patients. Several studies across the world are conducted to evaluate various candidate biomarkers for early detection of PD [8]- [10]. The subtle and poorly characterized symptoms of Parkinson's disease pose a significant challenge to early detection.…”

Section: Introductionmentioning

confidence: 99%

Improved Classification with Simultaneous Feature Selection of Speech Signals for Parkinson's Patients

Sharif

Siddique

Mumtaz

et al. 2021

VFAST trans. softw. eng.

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Parkinson's disease (PD) is a brain disorder occurs due to a deficiency of dopamine hormone that regulates activities of the human body. Generally, the disease can be diagnosed by clinicians through clinical observation where they categorized PD patients on a PD assessment scale to understand disease severity in order to define a therapy/treatment plan. The clinicians have a view that this approach is not suitable for diagnosis at an early stage of the disease. Recent research outcome has shown that PD patients exhibit vocal impairment at the early stage of the disease, and this is now becoming a benchmark for early PD detection. Often researchers employ state-of-the-art speech analysis techniques that exploit various extracted features to meet the objective. An optimal set of features that best explains the problem often requires careful attention to the selection of extracted features in use. As a general practice, data analysts have a view that it is better to collect as many features as possible related to the problem but at the same time, it is also believed that the presence of some noisy features can also compromise classification ability. Our main objective in this work is to select/identify the optimal set of features to utilize for the machine learning classification models with an objective to have an improved early PD detection in patients. The selection of optimal features set will not only help clinicians to quickly diagnose PD but will also be useful to develop a better patient care strategy at an early stage of PD. In this study, various experiment are conducted to observe the most contributing speech feature to classify PD patients. The study have showed by using the Best-First feature selection approach the most optimal features from the PD dataset can be achieved. The efficacy of our approach with the optimal set of features has shown an improvement in classification with an accuracy of 92.19% that is better than the earliest reported accuracy of 86% [23] for an almost similar number of features.

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Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

Cited by 6 publications

References 52 publications

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Alpha-Synuclein as a Biomarker of Parkinson’s Disease: Good, but Not Good Enough

Neuroinflammation In Parkinson’s Disease: A Study With [11C]PBR28 PET And Cerebrospinal Fluid Markers

Improved Classification with Simultaneous Feature Selection of Speech Signals for Parkinson's Patients

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