Blood Contamination in CSF and Its Impact on Quantitative Analysis of Alpha-Synuclein

Barkovits, Katalin; Kruse, Niels; Linden, Andreas; Tönges, Lars; Pfeiffer, Kathy; Mollenhauer, Brit; Marcus, Katrin

doi:10.3390/cells9020370

Cited by 37 publications

(38 citation statements)

References 34 publications

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“…Hypothetically, the presence of Lewy bodies (a common co-pathology in AD patients) could reduce CSF α-synuclein (as in PD), while the presence of synaptic or neuronal degeneration could increase CSF α-synuclein as an injury response 97 . A pre-analytical factor affecting CSF αsynuclein is that it is sensitive to blood-contamination, which gives false high levels 98 . The inconsistent results, the unclear biological role, and the pre-analytical variability may make it difficult to apply CSF α-synuclein as a biomarker.…”

Section: Levels Of Reproducibilitymentioning

confidence: 99%

Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies

et al. 2020

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Biomarkers have revolutionized scientific research on neurodegenerative diseases, in particular Alzheimer’s disease, transformed drug trial design, and are also increasingly improving patient management in clinical practice. A few key cerebrospinal fluid biomarkers have been robustly associated with neurodegenerative diseases. Several novel biomarkers are very promising, especially blood-based markers. However, many biomarker findings have had low reproducibility despite initial promising results. In this perspective, we identify possible sources for low reproducibility of studies on fluid biomarkers for neurodegenerative diseases, with a focus on Alzheimer’s disease. We suggest guidelines for researchers and journal editors, with the aim to improve reproducibility of findings.

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Section: Levels Of Reproducibilitymentioning

confidence: 99%

Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies

et al. 2020

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“…Thus, blood contamination during CSF acquisition might represent another source of variation, skewing the t-α-syn concentration results in CSF. 183,184 Despite the possible problems just discussed, there have been many studies evaluating α-syn as blood biomarker for dementias. Studies for α-syn in plasma and serum in PD have all shown similar conflicting results as in CSF.…”

Section: Pre-and Postsynaptic Biomarkersmentioning

confidence: 99%

“…Thus, blood contamination during CSF acquisition might represent another source of variation, skewing the t-α-syn concentration results in CSF. 183 , 184 …”

Section: Fluid Biomarkers For Synapse Pathologymentioning

confidence: 99%

Fluid Biomarkers for Synaptic Dysfunction and Loss

et al. 2020

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Synapses are the site for brain communication where information is transmitted between neurons and stored for memory formation. Synaptic degeneration is a global and early pathogenic event in neurodegenerative disorders with reduced levels of pre- and postsynaptic proteins being recognized as a core feature of Alzheimer’s disease (AD) pathophysiology. Together with AD, other neurodegenerative and neurodevelopmental disorders show altered synaptic homeostasis as an important pathogenic event, and due to that, they are commonly referred to as synaptopathies. The exact mechanisms of synapse dysfunction in the different diseases are not well understood and their study would help understanding the pathogenic role of synaptic degeneration, as well as differences and commonalities among them and highlight candidate synaptic biomarkers for specific disorders. The assessment of synaptic proteins in cerebrospinal fluid (CSF), which can reflect synaptic dysfunction in patients with cognitive disorders, is a keen area of interest. Substantial research efforts are now directed toward the investigation of CSF synaptic pathology to improve the diagnosis of neurodegenerative disorders at an early stage as well as to monitor clinical progression. In this review, we will first summarize the pathological events that lead to synapse loss and then discuss the available data on established (eg, neurogranin, SNAP-25, synaptotagmin-1, GAP-43, and α-syn) and emerging (eg, synaptic vesicle glycoprotein 2A and neuronal pentraxins) CSF biomarkers for synapse dysfunction, while highlighting possible utilities, disease specificity, and technical challenges for their detection.

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“…To this end, probes specifically targeting o-␣Syn with high sensitivity and high affinity hold great promise [214]. Of note, it is important to indicate here that higher CSF ␣Syn concentrations can be linked to blood contamination due to the expression of ␣Syn in erythrocytes [215], thereby requiring strict and rigorous markers for blood contamination and/or a standardized grade system for blood levels in CSF samples. Studies are also being performed to find molecules blocking the endocytosis of ␣Syn oligomers, thus preventing healthy cells from taking up pathogenic ␣Syn species, which could serve as a potential strategy for reducing oligomeric ␣Synmediated toxicity [214].…”

Section: Monotherapymentioning

confidence: 99%

Soluble endogenous oligomeric α-synuclein species in neurodegenerative diseases: Expression, spreading, and cross-talk

Kayed

Dettmer

Lesné

2020

JPD

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There is growing recognition in the field of neurodegenerative diseases that mixed proteinopathies are occurring at greater frequency than originally thought. This is particularly true for three amyloid proteins defining most of these neurological disorders, amyloid-beta (A␤), tau, and alpha-synuclein (␣Syn). The coexistence and often co-localization of aggregated forms of these proteins has led to the emergence of concepts positing molecular interactions and cross-seeding between A␤, tau, and ␣Syn aggregates. Amongst this trio, ␣Syn has received particular attention in this context during recent years due to its ability to modulate A␤ and tau aggregation in vivo, to interact at a molecular level with A␤ and tau in vivo and to cross-seed tau in mice. Here we provide a comprehensive, critical, and accessible review about the expression, role and nature of endogenous soluble ␣Syn oligomers because of recent developments in the understanding of ␣Syn multimerization, misfolding, aggregation, cross-talk, spreading and cross-seeding in neurodegenerative disorders, including Parkinson's disease, dementia with Lewy bodies, multiple system atrophy, Alzheimer's disease, and Huntington's disease. We will also discuss our current understanding about the relative toxicity of endogenous ␣Syn oligomers in vivo and in vitro, and introduce potential opportunities to counter their deleterious effects.

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Blood Contamination in CSF and Its Impact on Quantitative Analysis of Alpha-Synuclein

Cited by 37 publications

References 34 publications

Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies

Increasing the reproducibility of fluid biomarker studies in neurodegenerative studies

Fluid Biomarkers for Synaptic Dysfunction and Loss

Soluble endogenous oligomeric α-synuclein species in neurodegenerative diseases: Expression, spreading, and cross-talk

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