Rostrocaudal Dynamics of CSF Biomarkers

Tarnaris, Andrew; Toma, Ahmed K; Chapman, Miles D.; Petzold, Axel; Keir, Geoff; Kitchen, Neil; Watkins, Laurence

doi:10.1007/s11064-010-0374-1

Cited by 43 publications

(25 citation statements)

References 29 publications

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“…Tarnaris et al compared Aβ 42 levels in cisternal and lumbar CSF and found a small rostrocaudal gradient. 45 In contrast, work by the Blennow group utilizing serial sampling measurements of 10 ml CSF did not demonstrate a spinal gradient for Aβ 42 . 46, 47 Based on these studies, if a gradient does exist from the site of reabsorption to the lumbar sampling site, the effect will likely be small and result in slight underestimation of the CSF clearance by our theoretical calculations.…”

Section: Discussionmentioning

confidence: 91%

Amyloid‐β efflux from the central nervous system into the plasma

Roberts

Elbert

Kasten

et al. 2014

Annals of Neurology

229

161

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Objective The aim of this study was to measure the flux of amyloid-β (Aβ) across the human cerebral capillary bed in order to determine if transport into the blood is a significant mechanism of clearance for Aβ produced in the central nervous system (CNS). Methods Time-matched blood samples were simultaneously collected from a cerebral vein (including the sigmoid sinus, inferior petrosal sinus, and the internal jugular vein), femoral vein, and radial artery of patients undergoing Inferior Petrosal Sinus Sampling (IPSS). For each plasma sample, Aβ concentration was assessed by three assays and the venous to arterial Aβ concentration ratios were determined. Results Aβ concentration was increased by ~7.5% in venous blood leaving the CNS capillary bed compared to arterial blood, indicating efflux from the CNS into the peripheral blood (p < 0.0001). There was no difference in peripheral venous Aβ concentration compared to arterial blood concentration. Interpretation Our results are consistent with clearance of CNS-derived Aβ into the venous blood supply with no increase from a peripheral capillary bed. Modeling these results suggests that direct transport of Aβ across the blood-brain barrier accounts for ~25% of Aβ clearance, and reabsorption of cerebrospinal fluid Aβ accounts for ~25% of the total CNS Aβ clearance in humans.

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Section: Discussionmentioning

confidence: 91%

Amyloid‐β efflux from the central nervous system into the plasma

Roberts

Elbert

Kasten

et al. 2014

Annals of Neurology

229

161

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“…Due to a limited access to simultaneously collected lumbar and ventricular CSF samples, no information is available about the rostrocaudal distribution of neuroproteins in the CSF. So far, ventricular and lumbar CSF samples from different populations have been used to characterize the protein distribution in the CSF [4,24]. …”

Section: Discussionmentioning

confidence: 99%

Neuroprotein Dynamics in the Cerebrospinal Fluid: Intraindividual Concomitant Ventricular and Lumbar Measurements

Brandner¹,

Thaler²,

Lewczuk

et al. 2013

Eur Neurol

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Objective: The measurement of neuromarker/neuroproteins in the cerebrospinal fluid (CSF) is gaining increased popularity. However, insufficient information is available on the rostrocaudal distribution of neuroproteins in the CSF to guarantee an appropriate interpretation of ventricular versus lumbar concentrations. Methods: In 10 patients treated with both an external ventricular and a lumbar CSF drain, we collected concomitant CSF samples. We measured CSF concentrations of the glial S100B protein, the neuron-specific enolase (Cobas e411®; Roche Diagnostics), the leptomeningeal β-trace protein (BN Pro Spec®; Dade Behring/Siemens), and the blood-derived albumin (Immage; Beckman Coulter). Statistical analysis was performed with a paired Wilcoxon signed ranks test. Results: In patients with a free CSF circulation without any recent neurosurgical procedure, S100B and neuron-specific enolase concentrations did not differ between the ventricular and lumbar CSF while β-trace and albumin levels were significantly higher in the lumbar than in the ventricular CSF (p = 0.008 and p = 0.005). Following posterior fossa tumor surgery, all proteins accumulate in the lumbar CSF. Conclusion: For brain-derived proteins, we could not confirma rostrocaudal CSF gradient while lepto-meningeal and blood-derived proteins accumulate in the lumbar CSF. We conclude that for the interpretation of protein CSF concentrations, the source of the sample is of crucial importance.

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“…Interpretation of this data will need to be considered if the CSF was of ventricular or lumbar origin, as there is evidence of a rostrocaudal gradient with higher CSF GFAP levels in ventricular CSF (Tarnaris et al, 2010). Likewise, the presence of blood in the CSF was related to higher CSF GFAP levels in hydrocephalus (Naureen et al, 2013).…”

Section: Hydrocephalusmentioning

confidence: 97%

Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease

Petzold

2015

Brain Research

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This review on the role of glial fibrillary acidic protein (GFAP) as a biomarker for astroglial pathology in neurological diseases provides background to protein synthesis, assembly, function and degeneration. Qualitative and quantitative analytical techniques for the investigation of human tissue and biological fluid samples are discussed including partial lack of parallelism and multiplexing capabilities. Pathological implications are reviewed in view of immunocytochemical, cell-culture and genetic findings. Particular emphasis is given to neurodegeneration related to autoimmune astrocytopathies and to genetic gain of function mutations. The current literature on body fluid levels of GFAP in human disease is summarised and illustrated by disease specific meta-analyses. In addition to the role of GFAP as a diagnostic biomarker for chronic disease, there are important data on the prognostic value for acute conditions. The published evidence permits to classify the dominant GFAP signatures in biological fluids. This classification may serve as a template for supporting diagnostic criteria of autoimmune astrocytopathies, monitoring disease progression in toxic gain of function mutations, clinical treatment trials (secondary outcome and toxicity biomarker) and provide prognostic information in neurocritical care if used within well defined time-frames.

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Rostrocaudal Dynamics of CSF Biomarkers

Cited by 43 publications

References 29 publications

Amyloid‐β efflux from the central nervous system into the plasma

Amyloid‐β efflux from the central nervous system into the plasma

Neuroprotein Dynamics in the Cerebrospinal Fluid: Intraindividual Concomitant Ventricular and Lumbar Measurements

Glial fibrillary acidic protein is a body fluid biomarker for glial pathology in human disease

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