Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

Katayama, Takayuki; Sawada, Jun; Takahashi, Kihito; Yahara, Osamu

doi:10.3390/brainsci10070466

Cited by 31 publications

(19 citation statements)

References 70 publications

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“…The biochemical biomarkers for PD include a broad range of molecules that have been analyzed in CSF, blood, or other biological fluids. These include dopamine and its catabolites, several other types of amine or amino acid neurotransmitters, neuropeptides, oxidative damage markers, purine catabolite like uric acid, inflammatory markers, neurotrophic factors like brain-derived neurotrophic factor (BDNF), microRNAs, and several proteins known to be associated with the pathogenesis of PD and other neurodegenerative disorders, and all these have been discussed elaborately in multiple reviews and meta-analyses ( Jiménez-Jiménez et al, 2014 ; Emamzadeh and Surguchov, 2018 ; He et al, 2018 ; Wei et al, 2018 ; Jiang L. et al, 2019 ; Katayama et al, 2020 ). To avoid repetition and because no clinically useful blood or CSF biochemical biomarker specific for PD is still available, we will only briefly discuss a few of these biomarkers.…”

Section: Biomarkers Of Pdmentioning

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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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: Biomarkers Of Pdmentioning

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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“…Neuroimaging is complex and expensive so the availability of fluid biomarkers that could 1) distinguish Parkinson's disease from healthy controls and essential tremors, 2) discriminate the different parkinsonian syndromes, and 3) predict rates of disease progression and the likelihood of superadded dementia would be welcome. Categories of biomarkers that have been investigated in studies on PD cerebrospinal fluid (CSF) include dopamine and its metabolites, other neurotransmitters, markers of oxidative stress, inflammation and immunological activity, growth factors, and abnormally aggregated proteins involved in typical and atypical PD pathologies [5].…”

Section: Fluid Biomarkersmentioning

confidence: 99%

Imaging Familial and Sporadic Neurodegenerative Disorders Associated with Parkinsonism

Brooks

2021

Neurotherapeutics

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In this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson’s disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with nonmotor complications of PD are presented. The similarities and differences in imaging findings in Lewy body dementia, Parkinson’s disease dementia, and Alzheimer’s disease are discussed.

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“…This study did not reveal any signi cant changes in the CSF NSE level in MSA, and signi cant evidence of publication bias relating to this topic was detected. Recent studies have identi ed other potentially useful biomarkers of MSA, such as α-synuclein, neuro lament light chain, DJ-1, 8-hydroxyguanosine (8OHG), Flt3 (Fms-related tyrosine kinase) ligand, YKL-40 (CHI3L1), and ubiquitin carboxy-terminal hydrolase L1 (UCHL-1) [33]. Further studies are needed to identify the optimal molecular biomarkers of MSA.…”

Section: Nse Levels In Msamentioning

confidence: 99%

Meta-analysis of Cerebrospinal Fluid Neuron-specific Enolase Levels in Alzheimer’s Disease, Parkinson’s Disease, Dementia With Lewy Bodies, and Multiple System Atrophy

Katayama

Sawada

Takahashi

et al. 2020

Preprint

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Background: To investigate the usefulness of cerebrospinal fluid (CSF) neuron-specific enolase (NSE) levels as a candidate biomarker of neurodegeneration in Alzheimer’s disease (AD), Parkinson’s disease (PD), PD with dementia (PDD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA).Methods: We performed a systematic search of PubMed, the Cochrane Library, SCOPUS, and Google Scholar to find studies that investigated the CSF levels of NSE in AD, PD, DLB, and/or MSA. For each disease, we pooled all available data and performed a meta-analysis, and meta-regression analyses of age and sex were conducted when significant in the main analysis.Results: Twenty studies were included (13 for AD, 8 for PD/PDD/DLB, and 4 for MSA). Significantly elevated CSF NSE levels were detected in AD (Hedges’ g = 0.822, 95% confidence interval [95%CI]: 0.332 to 1.311, p = 0.0010), but the data exhibited high heterogeneity (I2 = 88.43%, p<0.001). The meta-regression analysis of AD showed that age (p<0.001), but not sex, had a significant effect on NSE. A meta-analysis of all the pooled data for PD/PDD/DLB did not show any significant changes in the CSF NSE level, but a sub-group analysis of PDD/DLB revealed significantly elevated CSF NSE levels (Hedges’ g = 0.507, 95%CI: 0.020 to 0.993, p = 0.0412). No significant changes in CSF NSE levels were detected in MSA.Conclusions: This study provided evidence about the usefulness of CSF NSE levels as a biomarker in AD and PDD/DLB, and age was found to affect the CSF NSE levels of AD patients.

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Cerebrospinal Fluid Biomarkers in Parkinson’s Disease: A Critical Overview of the Literature and Meta-Analyses

Cited by 31 publications

References 70 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

Imaging Familial and Sporadic Neurodegenerative Disorders Associated with Parkinsonism

Meta-analysis of Cerebrospinal Fluid Neuron-specific Enolase Levels in Alzheimer’s Disease, Parkinson’s Disease, Dementia With Lewy Bodies, and Multiple System Atrophy

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