Cerebrospinal Fluid Levels of 14-3-3 Gamma: What Does It Tell Us About Sporadic Creutzfeldt-Jakob Disease?

Pharmacology ◽  
2017 ◽  
Vol 100 (5-6) ◽  
pp. 243-245 ◽  
Author(s):  
Christian Humpel ◽  
Thomas Benke
Keyword(s):  
Cerebrospinal Fluid ◽  
High Risk ◽  
Retrospective Analysis ◽  
Short Report ◽  
Healthy Controls ◽  
Jakob Disease ◽  
Csf Levels ◽  
Fluid Levels ◽  
Very High ◽  
Probable Diagnosis

Clinical diagnosis of Creutzfeldt-Jakob disease (CJD) can be supported by the analysis of Tau and 14-3-3 in the cerebrospinal fluid (CSF). In this short report, we report about a retrospective analysis performed on 2,296 routinely collected CSF samples, and 44 samples with a ratio of phosphoTau181/Tau <0.075 were selected. Analysis was performed with a novel 14-3-3 gamma CircuLex Elisa. We show that control levels were around 6,000 AU/mL and samples from Alzheimer patients were not different from those collected from healthy controls. Four cases of verified CJD had 14-3-3 CSF levels of >100,000 AU/mL, while 10 out of 12 suspected CJD samples with 14-3-3 CSF levels between 50,000-100,000 AU/mL were CJD positive. All samples with 14-3-3 levels between 15,000 and 50,000 AU/mL were not CJD cases but disorders with complex neuropathology. In conclusion, our data suggests that in CSF samples with a phospho-Tau-181/Tau ratio <0.075 CSF levels of 14-3-3 should be analyzed. Our data suggests a very high risk for CJD with 14-3-3 levels above 100,000 AU/mL and a probable diagnosis of CJD based on laboratory parameters above 50,000 AU/mL.

scholarly journals Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

2021 ◽  
Vol 11 (2) ◽  
pp. 238
Author(s):  
Keld-Erik Byg ◽  
Helle H. Nielsen ◽  
Tobias Sejbaek ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chain ◽  
Plasma Levels ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Fluid Levels

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

Low CSF Concentrations of Cyclic GMP in Schizophrenia

1983 ◽  
Vol 142 (3) ◽  
pp. 288-291 ◽  
Author(s):  
W. F. Gattaz ◽  
H. Cramer ◽  
H. Beckmann
Keyword(s):  
Cerebrospinal Fluid ◽  
Cyclic Gmp ◽  
Homovanillic Acid ◽  
Healthy Controls ◽  
Neuroleptic Treatment ◽  
Cholinergic Activity ◽  
Schizophrenic Patients ◽  
Csf Levels

SummaryIncreasing evidence suggests that the concentrations of cyclic guanosine 3′5′-monophosphate (cGMP) in the cerebrospinal fluid (CSF) may reflect central cholinergic activity. When the concentrations of this nucleotide in the CSF from 28 schizophrenic patients (13 without and 15 with neuroleptic treatment) and 16 psychiatrically healthy controls was determined the schizophrenics showed significantly lower CSF levels of cGMP as compared to controls.As dopamine and homovanillic acid concentrations were not altered in these CSF samples, this finding of reduced cGMP suggests a cholinergic-dopaminergic imbalance in schizophrenia, with a reduction of the former and consequently a relative dominance of the latter.

[P2-227]: THE CEREBROSPINAL FLUID LEVELS OF TWO DNA AND RNA DAMAGE MARKERS ARE NOT SIGNIFICANTLY DIFFERENT IN A CROSS-SECTIONAL STUDY OF PATIENTS WITH AD, MCI, AND HEALTHY CONTROLS

2017 ◽  
Vol 13 (7S_Part_14) ◽  
pp. P698-P698
Author(s):  
Anja Hviid Simonsen ◽  
Allan Weimann ◽  
Christian Juel Jakobsen ◽  
Steen Gregers Hasselbalch ◽  
Gunhild Waldemar ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cross Sectional Study ◽  
Healthy Controls ◽  
Sectional Study ◽  
Cross Sectional ◽  
Cerebrospinal Fluid Levels ◽  
Dna And Rna ◽  
Rna Damage ◽  
Fluid Levels

IL-1β, IL-6, IL-10, and TNFα single nucleotide polymorphisms are associated with cerebrospinal fluid levels of biomarkers of Alzheimer’s disease

2019 ◽  
Author(s):  
Mirjana Babić Leko ◽  
Matea Nikolac Perković ◽  
Nataša Klepac ◽  
Dubravka Švob Štrac ◽  
Fran Borovečki ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Inflammatory Cytokines ◽  
Nucleotide Polymorphisms ◽  
Neuron Damage ◽  
Csf Levels ◽  
Factor Α ◽  
Fluid Levels ◽  
T Tau

Abstract Background Neuroinflammation plays an important role in Alzheimer’s disease (AD). During this process, activated microglia release pro-inflammatory cytokines such as interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor α (TNFα) that participate in neuron damage. However, anti-inflammatory cytokines (such as IL-10), which maintain homeostasis of immune response, are also released. Previous studies showed the association of IL-1α -889C/T (rs1800587), IL-1β -1473G/C (rs1143623), IL-6 -174C/G (rs1800795), IL-10 -1082G/A (rs1800896) and TNFα -308A/G (rs1800629) polymorphisms with AD.Methods In this study, we assessed whether people carrying certain genotypes in these polymorphisms are more prone to develop AD-related pathology, reflected by pathological levels of cerebrospinal fluid (CSF) AD biomarkers including amyloid β1–42 (Aβ1–42), total tau (t‐tau), tau phosphorylated at Thr 181 (p‐tau181), Ser 199 (p‐tau199), and Thr 231 (p‐tau231), and visinin‐like protein 1 (VILIP‐1). The study included 115 AD patients, 53 patients with mild cognitive impairment (MCI), 11 healthy controls, and 54 patients with other causes of dementia.Results A significant increase in p-tau CSF levels was found in patients with the AA IL-10 -1082G/A and GG TNFα -308A/G genotypes, and in carriers of a G allele in IL-1β -1473C/G and IL-6 -174C/G polymorphisms. T-tau levels were increased while Aβ1-42 levels were decreased in carriers of a G allele in IL-1β -1473C/G polymorphism. An increase in VILIP-1 levels was observed in patients with CG and GG IL-1β -1473C/G, GC IL-6 -174C/G and GG TNFα -308A/G genotype.Conclusions These results suggest that persons carrying certain genotypes in IL10 (-1082G/A), IL1β (1473C/G), IL6 (-174C/G) and TNFα (-308A/G) could be more vulnerable to development of neuroinglammation, and consequently of AD.

Soluble IL-6 receptors in the serum and cerebrospinal fluid of paranoid schizophrenic patients

1997 ◽  
Vol 12 (6) ◽  
pp. 294-299 ◽  
Author(s):  
N Müller ◽  
P Dobmeier ◽  
M Empl ◽  
M Riedel ◽  
M Schwarz ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Interleukin 6 ◽  
Serum Levels ◽  
Healthy Controls ◽  
Central Action ◽  
Neuroleptic Treatment ◽  
Interleukin 6 Receptor ◽  
Schizophrenic Patients ◽  
Csf Levels ◽  
Paranoid Schizophrenic

SummarySoluble Interleukin-6 receptor (sIL-6R) levels are strongly related to the levels of Interleukin-6 (IL-6), and sIL-6Rs increase the immune activating properties of IL-6. We estimated sIL-6R serum levels in 25 schizophrenic patients and 25 healthy controls. In the patients, SIL-6R-CSF levels were also measured. The psychopathology was rated according to the AMDP system. We found a significant correlation between serum and cerebrospinal fluid (CSF) levels of sIL-6R, suggesting that serum levels may be a meaningful marker for the central action of sIL-6R. Moreover, significant correlations between the paranoid-hallucinatory syndrome and sIL-6R levels both in serum and CSF were observed. This finding suggests that IL-6 plays a role in the paranoid-hallucinatory symptomatology in schizophrenia. This can be understood regarding the influence of IL-6 to the catecholaminergic neurotransmission. The downregulating effects of neuroleptic treatment to sIL-6R demonstrate that the sIL-6R levels are decreased in the whole group of schizophrenic patients compared to controls.

scholarly journals Imbalanced Kynurenine Pathway in Schizophrenia

2014 ◽  
Vol 7 ◽  
pp. IJTR.S16800 ◽  
Author(s):  
Magdalena E. Kegel ◽  
Maria Bhat ◽  
Elisabeth Skogh ◽  
Martin Samuelsson ◽  
Kristina Lundberg ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Cerebrospinal Fluid ◽  
Liquid Chromatography ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Kynurenine Pathway ◽  
The Other ◽  
Healthy Controls ◽  
Liquid Chromatography Mass Spectrometry ◽  
Csf Levels

Several studies suggest a role for kynurenic acid (KYNA) in the pathophysiology of schizophrenia. It has been proposed that increased brain KYNA levels in schizophrenia result from a pathological shift in the kynurenine pathway toward enhanced KYNA formation, away from the other branch of the pathway leading to quinolinic acid (QUIN). Here we investigate the levels of QUIN in cerebrospinal fluid (CSF) of patients with schizophrenia and healthy controls, and relate those to CSF levels of KYNA and other kynurenine metabolites from the same individuals. CSF QUIN levels from stable outpatients treated with olanzapine (n = 22) and those of controls (n = 26) were analyzed using liquid chromatography-mass spectrometry. No difference in CSF QUIN levels between patients and controls was observed (20.6 ± 1.5 nM vs. 18.2 ± 1.1 nM, P = 0.36). CSF QUIN was positively correlated to CSF kynurenine and CSF KYNA in patients but not in controls. The CSF QUIN/KYNA ratio was lower in patients than in controls ( P = 0.027). In summary, the present study offers support for an over-activated and imbalanced kynurenine pathway, favoring the production of KYNA over QUIN in patients with schizophrenia.

scholarly journals HIGHER LEVELS OF CEREBROSPINAL FLUID NITRITE AND NITRATE IN LEVODOPA-INDUCED DYSKINESIAS IN PARKINSON’S DISEASE

2020 ◽  
Author(s):  
Bruno L. Santos-Lobato ◽  
Mariza Bortolanza ◽  
Marcelo E. Batalhão ◽  
Ângela V. Pimentel ◽  
Evelin Capellari-Carnio ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
List Type ◽  
Healthy Controls ◽  
Clinical Variables ◽  
Csf Levels ◽  
Nitric Oxide Metabolites

AbstractIntroductionLevodopa-induced dyskinesias (LID) in Parkinson’s disease (PD) are frequent complications, and nitric oxide has a role on its pathophysiology. The present work aims to investigate CSF levels of nitric oxide metabolites nitrite and nitrate (NOx) in patients with PD and LID.MethodsWe measured CSF NOx levels in patients with PD with and without LID, and in healthy controls. The levels of CSF NOx levels were measured by ozone-based chemiluminescence.Results67 participants were enrolled. CSF NOx levels were higher in patients with PD with LID than in healthy controls (Kruskal-Wallis statistics = 7.24, p = 0.02). CSF NOx levels did not correlate with other clinical variables.ConclusionWe reported higher levels of nitric oxide in the CSF of patients with PD and LID.Highlights–Nitric oxide has a role on levodopa-induced dyskinesias in Parkinson’s disease–We measured CSF nitrite and nitrate in Parkinson’s disease patients with dyskinesias–CSF nitrite and nitrate were higher in Parkinson’s disease patients with dyskinesias

scholarly journals Evaluation of Human Cerebrospinal Fluid Malate Dehydrogenase 1 as a Marker in Genetic Prion Disease Patients

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 800 ◽  
Author(s):  
Inga Zerr ◽  
Anna Villar-Piqué ◽  
Vanda Edit Schmitz ◽  
Anna Poleggi ◽  
Maurizio Pocchiari ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Malate Dehydrogenase ◽  
Prion Disease ◽  
Area Under The Curve ◽  
Correlation Study ◽  
Enzyme Linked Immunosorbent Assay ◽  
Marker Proteins ◽  
Jakob Disease ◽  
Csf Levels ◽  
Mitochondrial Malate Dehydrogenase

The exploration of accurate diagnostic markers for differential diagnosis of neurodegenerative diseases is an ongoing topic. A previous study on cerebrospinal fluid (CSF)-mitochondrial malate dehydrogenase 1 (MDH1) in sporadic Creutzfeldt–Jakob disease (sCJD) patients revealed a highly significant upregulation of MDH1. Here, we measured the CSF levels of MDH1 via enzyme-linked immunosorbent assay in a cohort of rare genetic prion disease cases, such as genetic CJD (gCJD) cases, exhibiting the E200K, V210I, P102L (Gerstmann–Sträussler–Scheinker syndrome (GSS)), or D178N (fatal familial insomnia (FFI)) mutations in the PRNP. Interestingly, we observed enhanced levels of CSF-MDH1 in all genetic prion disease patients compared to neurological controls (without neurodegeneration). While E200K and V210I carriers showed highest levels of MDH1 with diagnostic discrimination from controls of 0.87 and 0.85 area under the curve (AUC), FFI and GSS patients exhibited only moderately higher CSF-MDH1 levels than controls. An impact of the PRNP codon 129 methionine/valine (MV) genotype on the amount of MDH1 could be excluded. A correlation study of MDH1 levels with other neurodegenerative marker proteins revealed a significant positive correlation between CSF-MDH1 concentration with total tau (tau) but not with 14-3-3 in E200K, as well as in V210I patients. In conclusion, our study indicated the potential use of MDH1 as marker for gCJD patients which may complement the current panel of diagnostic biomarkers.

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