| 1. |
- Bergman, Lina, 1982, et al.
(författare)
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Cerebral biomarkers in neurologic complications of preeclampsia
- 2022
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Ingår i: American Journal of Obstetrics and Gynecology. - : Elsevier BV. - 0002-9378 .- 1097-6868. ; 227:2, s. 298.e1-298.e10
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is no tool to accurately predict who is at risk of developing neurologic complications of preeclampsia, and there is no objective method to determine disease severity. Objective: We assessed whether plasma concentrations of the cerebral biomarkers neurofilament light, tau, and glial fibrillary acidic protein could reflect disease severity in several phenotypes of preeclampsia. Furthermore, we compared the cerebral biomarkers with the angiogenic biomarkers soluble fms-like tyrosine kinase 1, placental growth factor, and soluble endoglin. Study Design: In this observational study, we included women from the South African Preeclampsia Obstetric Adverse Events biobank. Plasma samples taken at diagnosis (preeclampsia cases) or admission for delivery (normotensive controls) were analyzed for concentrations of neurofilament light, tau, glial fibrillary acidic protein, placental growth factor, soluble fms-like tyrosine kinase 1, and soluble endoglin. The cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age, and parity. Results: Compared with 28 women with normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of neurofilament light (95% confidence interval, 1.64–2.88), 2.17-fold higher tau (95% confidence interval, 1.49–3.16), and 2.77-fold higher glial fibrillary acidic protein (95% confidence interval, 2.06–3.72). Overall, 72 women with neurologic complications (eclampsia, cortical blindness, and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher; 95% confidence interval, 1.92–4.65) and glial fibrillary acidic protein (3.22-fold higher; 95% confidence interval, 2.06–5.02) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications (n=31). Moreover, angiogenic markers were higher, but to a lesser extent. Women with hemolysis, elevated liver enzymes, and low platelet count (n=20) demonstrated increased plasma concentrations of neurofilament light (1.64-fold higher; 95% confidence interval, 1.06–2.55), tau (4.44-fold higher; 95% confidence interval, 1.85–10.66), and glial fibrillary acidic protein (1.82-fold higher; 95% confidence interval, 1.32–2.50) compared with women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications. There was no difference shown in the angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema; hemolysis, elevated liver enzymes, and low platelet count; or neurologic complications for any of the biomarkers. Plasma concentrations of tau and glial fibrillary acidic protein were increased in women with several neurologic complications compared with women with eclampsia only. Conclusion: Plasma neurofilament light, glial fibrillary acidic, and tau were candidate biomarkers for the diagnosis and possibly prediction of cerebral complications of preeclampsia.
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| 2. |
- Bromander, Sara, et al.
(författare)
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Cerebrospinal fluid insulin during non-neurological surgery.
- 2010
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Ingår i: J Neural Transm (Vienna, Austria:1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 20, s. 328-329
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Tidskriftsartikel (refereegranskat)abstract
- Insulin plays an important metabolic and transmitter role in the central nervous system, but few studies have investigated the relationship between central and peripheral insulin concentrations. 35 patients undergoing knee surgery had cerebrospinal fluid (CSF) samples drawn before, 3 h after, and in the morning following surgery. Serum insulin concentrations increased after surgery and CSF insulin concentrations changed in the same direction with far smaller amplitude. These results indicate that the blood-brain barrier protects the brain from stress-induced peripheral hormonal fluctuations.
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| 3. |
- Hallén, Tobias, et al.
(författare)
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Circulating brain injury biomarkers increase after endoscopic surgery for pituitary tumors.
- 2021
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Ingår i: Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. - : Elsevier BV. - 1532-2653. ; 89, s. 113-121
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Tidskriftsartikel (refereegranskat)abstract
- Pituitary tumors and subsequent treatment with endoscopic transsphenoidal surgery (ETSS) may cause injury to suprasellar structures, causing long-term fatigue and neurocognitive impairment. A method to quantify brain injury after ETSS is not available. In this prospective, exploratory study of patients undergoing ETSS for pituitary tumors, a novel approach to detect possible neuronal damage is presented. Plasma concentrations of brain injury biomarkers (glial fibrillary acidic protein [GFAP], tau, and neurofilament light [NFL]) were measured the day before surgery, immediately after surgery, at day 1 and 5, and at 6 and 12 months after surgery, using enzyme-linked immunosorbent assays. The association between the increase of biomarkers with preoperative tumor extension and postoperative patient-perceived fatigue was evaluated. Suprasellar tumor extension was assessed from MRI scans, and self-perceived fatigue was assessed using the Multidimensional Fatigue Inventory before and 6 months after surgery. Thirty-five patients were included in the analysis. Compared to baseline, GFAP showed a maximal increase at day 1 after surgery (p = 0.0005), tau peaked postoperatively on the day of surgery (p = 0.019), and NFL reached its maximum at day 5 after surgery (p < 0.0001). The increase in GFAP correlated with preoperative chiasmal compression (p = 0.020). The increase in tau was correlated with preoperative chiasmal (p = 0.011) and hypothalamus compression (p = 0.016), and fatigue score 6 months after surgery (p = 0.016). In conclusion, the concentrations of brain injury biomarkers in blood increased after ETSS for pituitary tumors. The results indicate that postoperative plasma GFAP and tau might reflect astroglial and neuronal damage after ETSS.
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| 4. |
- Novakova, Lenka, et al.
(författare)
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Searching for neurodegeneration in multiple sclerosis at clinical onset: Diagnostic value of biomarkers
- 2018
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Background Neurodegeneration occurs during the early stages of multiple sclerosis. It is an essential, devastating part of the pathophysiology. Tools for measuring the degree of neurodegeneration could improve diagnostics and patient characterization. Objective This study aimed to determine the diagnostic value of biomarkers of degeneration in patients with recent clinical onset of suspected multiple sclerosis, and to evaluate these biomarkers for characterizing disease course. Methods This cross-sectional study included 271 patients with clinical features of suspected multiple sclerosis onset and was the baseline of a prospective study. After diagnostic investigations, the patients were classified into the following disease groups: Patients with clinically isolated syndrome (n = 4) or early relapsing remitting multiple sclerosis (early RRMS; n = 93); patients with relapsing remitting multiple sclerosis with disease durations ≥2 years (established RRMS; n = 39); patients without multiple sclerosis, but showing symptoms (symptomatic controls; n = 89); and patients diagnosed with other diseases (n = 46). In addition, we included healthy controls (n = 51) and patients with progressive multiple sclerosis (n = 23). We analyzed six biomarkers of neurodegeneration: Cerebrospinal fluid neurofilament light chain levels; cerebral spinal fluid glial fibrillary acidic protein; cerebral spinal fluid tau; retinal nerve fiber layer thickness; macula volume; and the brain parenchymal fraction. Results Except for increased cerebral spinal fluid neurofilament light chain levels, median 670 ng/L (IQR 400-2110), we could not find signs of early degeneration in the early disease group with recent clinical onset. However, the intrathecal immunoglobin G production and cerebral spinal fluid neurofilament light chain levels showed diagnostic value. Moreover, elevated levels of cerebral spinal fluid glial fibrillary acidic protein, thin retinal nerve fiber layers, and low brain parenchymal fractions were associated with progressive disease, but not with the other phenotypes. Thin retinal nerve fiber layers and low brain parenchymal fractions, which indicated neurodegeneration, were associated with longer disease duration. Conclusions In clinically suspected multiple sclerosis, intrathecal immunoglobin G production and neurofilament light chain levels had diagnostic value. Therefore, these biomarkers could be included in diagnostic work-ups for multiple sclerosis. We found that the thickness of the retinal nerve fiber layer and the brain parenchymal fraction were not different between individuals that were healthy, symptomatic, or newly diagnosed with multiple sclerosis. This finding suggested that neurodegeneration had not reached a significant magnitude in patients with a recent clinical onset of multiple sclerosis.
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| 5. |
- von Otter, Malin, 1978, et al.
(författare)
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Nrf2-encoding NFE2L2 haplotypes influence disease progression but not risk in Alzheimer's disease and age-related cataract
- 2010
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Ingår i: Mechanisms of Ageing and Development. - : Elsevier BV. - 0047-6374 .- 1872-6216. ; 131:2, s. 105-110
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease (AD) and age-related cataract, disorders characterized by protein aggregation causing late-onset disease, both involve oxidative stress. We hypothesize that common variants of NFE2L2 and KEAP1, the genes encoding the main regulators of the Nrf2 system, an important defence system against oxidative stress, may influence risk of AD and/or age-related cataract. This case-control study combines an AD material (725 cases and 845 controls), and a cataract material (489 cases and 182 controls). Genetic variation in NFE2L2 and KEAP1 was tagged by eight and three tag single nucleotide polymorphisms (SNPs), respectively. Single SNPs and haplotypes were analyzed for associations with disease risk, age parameters, MMSE and AD cerebrospinal fluid biomarkers. NFE2L2 and KEAP1 were not associated with risk of AD or cataract. However, one haplotype allele of NFE2L2 was associated with 2 years earlier age at AD onset (pc 0.013) and 4 years earlier age at surgery for posterior subcapsular cataract (p(c) = 0.019). Another haplotype of NFE2L2 was associated with 4 years later age at surgery for cortical cataract (p(c) = 0.009). Our findings do not support NFE2L2 or KEAP1 as susceptibility genes for AD or cataract. However, common variants of the NFE2L2 gene may affect disease progression, potentially altering clinically recognized disease onset. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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| 6. |
- Daborg, Jonny, et al.
(författare)
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Complement Gene Single Nucleotide Polymorphisms and Biomarker Endophenotypes of Alzheimer's Disease
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877. ; 35:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- The complement system has been implicated in both physiological synapse elimination and Alzheimer's disease (AD). Here, we investigated associations between four single nucleotide polymorphisms (SNPs) in complement genes and cerebrospinal fluid (CSF) biomarkers for AD in 452 neurochemically or neuropathologically verified AD cases and 678 cognitively normal controls. None of the SNPs associated with risk of AD but there were potential associations of rs9332739 in the C2 gene and rs4151667 in the complement factor B gene with CSF tau levels (p = 0.023) and Mini-Mental State Examination scores (p = 0.012), both of which may be considered markers of disease intensity/severity.
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| 7. |
- Abramsson, Alexandra, 1973, et al.
(författare)
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No Association of LOXL1 Gene Polymorphisms with Alzheimer's Disease
- 2011
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 13:2, s. 160-166
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Tidskriftsartikel (refereegranskat)abstract
- Aggregation of amyloid-beta is one of the major characteristics in brains of patients with Alzheimer's disease (AD). Although several mechanisms behind the formation of such aggregates have been suggested the regulatory factors are still unknown. The present study aimed at investigating the association of lysyl oxidase-like 1 (LOXL1) polymorphisms with AD diagnosis and cerebrospinal fluid biomarkers (CSF) for the disease. Proteins of the lysyl oxidase (LOX) family are involved in cross-linking extracellular matrix proteins to insoluble fibers and have been associated with neurodegenerative diseases including AD. Genetic polymorphisms in LOXL1 (rs1048661, rs3825942, and rs2165241) have been linked to exfoliation syndrome and exfoliation glaucoma, conditions that have shown association with AD. The polymorphisms were genotyped by Taqman allelic discrimination in a study sample including AD patients (n = 318) and controls (n = 575). In a subgroup of the population, the polymorphisms were analyzed in relation to APOE epsilon 4 genotype and to CSF (T-tau, P-tau, and A beta(1-42)). No evidence for associations of these polymorphisms with risk for AD or any of the studied CSF biomarkers measured was found. These results do not support LOXL1 as being a major risk gene for AD.
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| 8. |
- Hesse, Camilla, et al.
(författare)
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The N-terminal domain of α-dystroglycan is released as a 38kDa protein and is increased in cerebrospinal fluid in patients with Lyme neuroborreliosis.
- 2011
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Ingår i: Biochemical and biophysical research communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 412:3
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Tidskriftsartikel (refereegranskat)abstract
- α-Dystroglycan is an extracellular adhesion protein that is known to interact with different ligands. The interaction is thought to stabilize the integrity of the plasma membrane. The N-terminal part of α-dystroglycan may be proteolytically processed to generate a small 38kDa protein (α-DG-N). The physiological significance of α-DG-N is unclear but has been suggested to be involved in nerve regeneration and myelination and to function as a potential biomarker for neurodegenerative and neuromuscular diseases. In this report we show that α-DG-N is released into different body fluids, such as lachrimal fluid, cerebrospinal fluid (CSF), urine and plasma. To investigate the significance of α-DG-N in CSF we examined the levels of α-DG-N and known neurodegenerative markers in CSF from patients diagnosed with Lyme neuroborreliosis (LNB) and healthy controls. In untreated acute phase LNB patients, 67% showed a significant increase of CSF α-DG-N compared to healthy controls. After treatment with antibiotics the CSF α-DG-N levels were normalized in the LNB patients.
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| 9. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Reduced cerebrospinal fluid BACE1 activity in multiple sclerosis.
- 2009
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Ingår i: Multiple sclerosis (Houndmills, Basingstoke, England). - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 15:4, s. 448-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Cell and animal experiments have shown that beta-site APP-cleaving enzyme 1 (BACE1) may be involved in myelination. OBJECTIVE: Here, we assess the association of cerebrospinal fluid (CSF) BACE1 activity with multiple sclerosis (MS). METHODS: BACE1 activity and levels of secreted amyloid precursor protein (APP) and amyloid-beta (Abeta) isoforms were analyzed in CSF from 100 patients with MS and 114 neurologically healthy controls. Patients with systemic lupus erythematosus (SLE), 26 with and 41 without cerebral engagement, were also included to enable comparisons with regards to another autoimmune disease. A subset of patients with MS and controls underwent a second lumbar puncture after 10 years. RESULTS: MS patients had lower CSF BACE1 activity than controls (P = 0.03) and patients with cerebral SLE (P < 0.001). Patients with cerebral SLE had higher BACE1 activity than any other group (P < 0.05 for all comparisons). BACE1 activity correlated with the different amyloid markers in all study groups. BACE1 activity decreased over 10 years in the MS group (P = 0.039) and correlated weakly with clinical disease severity scores in an inverse manner. CONCLUSIONS: These results suggest an involvement of BACE1 in the MS disease process.
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| 10. |
- von Otter, Malin, 1978, et al.
(författare)
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Kinesin Light Chain 1 Gene Haplotypes in Three Conformational Diseases
- 2010
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Ingår i: NeuroMolecular Medicine. - : Springer Science and Business Media LLC. - 1535-1084 .- 1559-1174. ; 12:3, s. 229-236
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Tidskriftsartikel (refereegranskat)abstract
- A functional intracellular transport system is essential to maintain cell shape and function especially in elongated cells, e.g. neurons and lens fibre cells. Impaired intracellular transport has been suggested as a common pathological mechanism for age-related diseases characterised by protein aggregation. Here, we hypothesise that common genetic variation in the transport protein kinesin may influence the risk of Parkinson's disease (PD), Alzheimer's disease (AD) and age-related cataract. This case-control study involves a PD material (165 cases and 190 controls), an AD material (653 cases and 845 controls) and a cataract material (495 cases and 183 controls). Genetic variation in the kinesin light chain 1-encoding gene (KLC1) was tagged by six tag single nucleotide polymorphisms (SNPs). Single SNPs and haplotypes were analysed for associations with disease risk, age parameters, mini-mental state examination scores and cerebrospinal fluid biomarkers for AD using logistic or linear regression. Genetic variation in KLC1 did not influence risk of PD. Weak associations with risk of AD were seen for rs8007903 and rs3212079 (P (c) = 0.04 and P (c) = 0.02, respectively). Two SNPs (rs8007903 and rs8702) influenced risk of cataract (P (c) = 0.0007 and P (c) = 0.04, respectively). However, the allele of rs8007903 that caused increased risk of AD caused reduced risk of cataract, speaking against a common functional effect of this particular SNP in the two diseases. Haplotype analyses did not add significantly to the associations found in the single SNP analyses. Altogether, these results do not convincingly support KLC1 as a major susceptibility gene in any of the studied diseases, although there is a small effect of KLC1 in relation to cataract.
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