| 11. |
- Cicognola, Claudia, et al.
(författare)
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No diurnal variation of classical and candidate biomarkers of Alzheimer's disease in CSF
- 2016
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Ingår i: Molecular Neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebrospinal fluid (CSF) biomarkers have gained increasing importance in the diagnostic work-up of Alzheimer's disease (AD). The core CSF biomarkers related to AD pathology (A beta 42, t-tau and p-tau) are currently used in CSF diagnostics, while candidate markers of amyloid metabolism (A beta 38, A beta 40, sAPP alpha, sAPP beta), synaptic loss (neurogranin), neuroinflammation (YKL-40), neuronal damage (VILIP-1) and genetic risk (apolipoprotein E) are undergoing evaluation. Diurnal fluctuation in the concentration of CSF biomarkers has been reported and may represent a preanalytical confounding factor in the laboratory diagnosis of AD. The aim of the present study was to investigate the diurnal variability of classical and candidate CSF biomarkers in a cohort of neurosurgical patients carrying a CSF drainage. Method: Samples were collected from a cohort of 13 neurosurgical patients from either ventricular (n = 6) or lumbar (n = 7) CSF drainage at six time points during the day, 1-7 days following the neurosurgical intervention. Concentrations of the core biomarkers were determined by immunoassays. Results: Although absolute values largely varied among subjects, none of the biomarkers showed significant diurnal variation. Site of drainage (lumbar vs. ventricular) did not influence this result. The different immunoassays used for tau and A beta markers provided similar results. Conclusion: Time of day at CSF collection does not ultimately affect the concentration levels of classical and candidate AD biomarkers. Similar trends were found when using different immunoassays, thus corroborating the consistency of the data.
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| 12. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies.
- 2017
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 306, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.
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| 13. |
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| 14. |
- Edsbagge, Mikael, et al.
(författare)
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Alzheimer's Disease-Associated Cerebrospinal Fluid (CSF) Biomarkers do not Correlate with CSF Volumes or CSF Production Rate.
- 2017
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Ingår i: Journal of Alzheimer's disease : JAD. - : IOS Press. - 1875-8908 .- 1387-2877. ; 58:3, s. 821-828
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Tidskriftsartikel (refereegranskat)abstract
- Neuropathologically, Alzheimer's disease (AD) is characterized by accumulation of a 42 amino acid peptide called amyloid-β (Aβ42) in extracellular senile plaques together with intraneuronal inclusions of hyperphosphorylated tau protein in neurofibrillary tangles and neuronal degeneration. These changes are reflected in the cerebrospinal fluid (CSF), the volumes and production rates of which vary considerably between individuals, by reduced concentration of Aβ42, increased concentration of phosphorylated tau (P-tau) protein, and increased concentration of total tau (T-tau) protein, respectively.To examine the outstanding question if CSF concentrations of AD associated biomarkers are influenced by variations in CSF volumes, CSF production rate, and intracranial pressure in healthy individuals.CSF concentrations of Aβ42, P-tau, and T-tau, as well as a number of other AD-related CSF biomarkers were analyzed together with intracranial subarachnoid, ventricular, and spinal CSF volumes, as assessed by magnetic resonance imaging volumetric measurements, and CSF production rate in 19 cognitively normal healthy subjects (mean age 70.6, SD 3.6 years).Negative correlations were seen between the concentrations of three CSF biomarkers (albumin ratio, Aβ38, and Aβ40), and ventricular CSF volume, but apart from this finding, no significant correlations were observed.These results speak against inter-individual variations in CSF volume and production rate as important confounds in the AD biomarker research field.
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| 15. |
- Fernström, Erik, et al.
(författare)
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Cerebrospinal fluid markers of extracellular matrix remodelling, synaptic plasticity and neuroinflammation before and after cranial radiotherapy
- 2018
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820. ; 284:2, s. 211-225
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Tidskriftsartikel (refereegranskat)abstract
- Background Advances in the treatment of brain tumours have increased the number of long-term survivors, but at the cost of side effects following cranial radiotherapy ranging from neurocognitive deficits to outright tissue necrosis. At present, there are no tools reflecting the molecular mechanisms underlying such side effects, and thus no means to evaluate interventional effects after cranial radiotherapy. Therefore, fluid biomarkers are of great clinical interest. Objective Cerebrospinal fluid (CSF) levels of proteins involved in inflammatory signalling, synaptic plasticity and extracellular matrix (ECM) integrity were investigated following radiotherapy to the brain. Methods Patients with small-cell lung cancer (SCLC) eligible for prophylactic cranial irradiation (PCI) were asked to participate in the study. PCI was prescribed either as 2 Gy/fraction to a total dose of 30 Gy (limited disease) or 4 Gy/fraction to 20 Gy (extensive disease). CSF was collected by lumbar puncture at baseline, 3 months and 1 year following PCI. Protein concentrations were measured using immunobased assays or mass spectrometry. Results The inflammatory markers IL-15, IL-16 and MCP-1/CCL2 were elevated in CSF 3 months following PCI compared to baseline. The plasticity marker GAP-43 was elevated 3 months following PCI, and the same trend was seen for SNAP-25, but not for SYT1. The investigated ECM proteins, brevican and neurocan, showed a decline following PCI. There was a strong correlation between the progressive decline of soluble APP and brevican levels. Conclusion To our knowledge, this is the first time ECM-related proteins have been shown to be affected by cranial radiotherapy in patients with cancer. These findings may help us to get a better understanding of the mechanisms behind side effects following radiotherapy.
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| 16. |
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| 17. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Plasma Concentration of the Neurofilament Light Protein (NFL) is a Biomarker of CNS Injury in HIV Infection: A Cross-Sectional Study
- 2016
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Ingår i: EBioMedicine. - : Elsevier BV. - 2352-3964. ; 3, s. 135-140
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cerebrospinal fluid (CSF) neurofilament light chain protein (NFL) is a sensitive marker of neuronal injury in a variety of neurodegenerative conditions, including the CNS dysfunction injury that is common in untreated HIV infection. However, an important limitation is the requirement for lumbar puncture. For this reason, a sensitive and reliable blood biomarker of CNS injury would represent a welcome advance in both clinical and research settings. Methods: To explore whether plasma concentrations of NFL might be used to detect CNS injury in HIV infection, an ultrasensitive Single molecule array (Simoa) immunoassay was developed. Using a cross-sectional design, we measured NFL in paired CSF and plasma samples from 121 HIV-infected subjects divided into groups according to stage of their systemic disease, presence of overt HIV-associated dementia (HAD), and after antiretroviral treatment (ART)-induced viral suppression. HIV-negative controls were also examined. Findings: Plasma and CSF NFL concentrations were very highly correlated (r=0.89, P<0.0001). While NFL was more than 50-fold lower plasma than CSF it was within the quantifiable range of the new plasma assay in all subjects, including the HIV negatives and the HIV positives with normal CSF NFL concentrations. The pattern of NFL changes were almost identical in plasma and CSF, both exhibiting similar age-related increases in concentrations along with highest values in HAD and substantial elevations in ART-naïve neuroasymptomatic subjects with low blood CD4+ T cells. Interpretation: These results show that plasma NFL may prove a valuable tool to evaluate ongoing CNS injury in HIV infection that may be applied in the clinic and in research settings to assess the presence if active CNS injury. Because CSF NFL is also elevated in a variety of other CNS disorders, sensitive measures of plasma NFL may similarly prove useful in other settings.
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| 18. |
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| 19. |
- Gustavsson, Carolina, et al.
(författare)
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Cerebrospinal fluid levels of insulin, leptin, and agouti-related protein in relation to BMI in pregnant women
- 2016
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 24:6, s. 1299-1304
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveDuring pregnancy, metabolic interactions must be adapted, though neuroendocrine mechanisms for increased food intake are poorly understood. The objective of this study was to characterize differences in insulin, leptin, and agouti-related protein (AgRP) levels in serum and cerebrospinal fluid (CSF) in pregnant women with normal weight (NW) and pregnant women with overweight (OW) or obesity (OB). Placenta as a source for increased peripheral AgRP levels during pregnancy was also investigated. MethodsWomen were recruited at admission for elective cesarean section. Insulin, AgRP, and leptin were measured in serum and CSF from 30 NW, 25 OW, and 21 OB at term. Serum during pregnancy and placenta at term were collected for further AgRP analysis. ResultsImmunohistology showed placental production of AgRP and serum AgRP levels increased throughout pregnancy. CSF AgRP, leptin, and insulin levels were higher in OW and OB than NW. Serum leptin and insulin levels were higher and AgRP lower in OB than NW. ConclusionsHigh serum AgRP levels might protect from the suppressive effects of leptin during pregnancy. Pregnant women with OB and OW might further be protected from the suppressive effect of leptin by high CSF AgRP levels. Evidence was found, for the first time, of human placental AgRP production mirrored by levels in the circulation.
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| 20. |
- Hall, Ulrika Andersson, et al.
(författare)
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Central and Peripheral Leptin and Agouti-Related Protein during and after Pregnancy in Relation to Weight Change.
- 2018
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Ingår i: Clinical endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 88:2, s. 263-271
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Tidskriftsartikel (refereegranskat)abstract
- To study changes of neuropeptides and adipokines in cerebrospinal fluid (CSF) and serum from pregnancy to post-pregnancy in relation to weight changes, fat mass and glucose metabolism.With high postpartum weight retention being a risk factor in future pregnancies and of life-long obesity we evaluated neuropeptide and adipokine changes in women who either gained weight or were weight stable.Women were followed for 5±1 years after pregnancy and divided into two groups, Weight-Stable and Weight-Gain, by weight change from start of pregnancy.Twenty-five women (BMI 27±5kg/m2 ) recruited at admission for elective caesarean section.CSF and serum levels of agouti-related protein (AgRP), leptin, and insulin, and serum levels of adiponectin and soluble leptin receptor were measured during and after pregnancy. These measurements were further related to fat mass and insulin sensitivity (HOMA-IR).S-AgRP levels during pregnancy were lower in the Weight-Stable group and a 1 unit increase in s-AgRP was associated with 24% higher odds of pertaining to the Weight-Gain group. After pregnancy, s-AgRP increased in the Weight-Stable group but decreased in the Weight-Gain group. Decreased transport of leptin into CSF during pregnancy was reversed by an increased CSF:serum leptin ratio after pregnancy. In women who returned to their pre-pregnancy weight, serum adiponectin increased after pregnancy and correlated negatively with HOMA-IR.S-AgRP concentration in late pregnancy may be one factor predicting weight change after pregnancy, and circulating AgRP may be physiologically important in the long-term regulation of body weight. This article is protected by copyright. All rights reserved.
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