| 1. |
- 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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| 2. |
- 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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| 3. |
- Bjursten, Sara, et al.
(författare)
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Early rise in brain damage markers and high ICOS expression in CD4+and CD8+T cells during checkpoint inhibitor-induced encephalomyelitis
- 2021
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Ingår i: Journal for Immunotherapy of Cancer. - : BMJ. - 2051-1426. ; 9:7
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Tidskriftsartikel (refereegranskat)abstract
- We report a case of rapid eradication of melanoma brain metastases and simultaneous near-fatal encephalomyelitis following double immune checkpoint blockade. Brain damage marker S-100B and C reactive protein increased before symptoms or signs of encephalomyelitis and peaked when the patient fell into a coma. At that point, additional brain damage markers and peripheral T cell phenotype was analyzed. The analyses were repeated four times during the patient's recovery. Axonal damage marker neurofilament light polypeptide (NFL) and astrocytic damage marker glial fibrillar acidic protein (GFAP) were very high in blood and cerebrospinal fluid and gradually normalized after immunosuppression and intensive care. The costimulatory receptor inducible T cell costimulatory receptor (ICOS) was expressed on a high proportion of CD4+ and CD8+T cells as encephalomyelitis symptoms peaked and then gradually decreased in parallel with clinical improvement. Both single and double immune checkpoint inhibitor-treated melanoma patients with other serious immune-related adverse events (irAE) (n=9) also expressed ICOS on a significantly higher proportion of CD4+ and CD8+T cells compared with controls without irAE (n=12). In conclusion, our results suggest a potential role for ICOS on CD4+ and CD8+T cells in mediating encephalomyelitis and other serious irAE. In addition, brain damage markers in blood could facilitate early diagnosis of encephalitis.
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| 4. |
- Trupp, Miles, et al.
(författare)
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Metabolite and peptide levels in plasma and CSF differentiating healthy controls from patients with newly diagnosed Parkinson's disease
- 2014
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Ingår i: Journal of Parkinson's Disease. - : Taylor & Francis. - 1877-7171 .- 1877-718X. ; 4:3, s. 549-560
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a progressive, multi-focal neurodegenerative disease for which there is no effective disease modifying treatment. A critical requirement for designing successful clinical trials is the development of robust and reproducible biomarkers identifying PD in preclinical stages. Objective: To investigate the potential for a cluster of biomarkers visualized with multiple analytical platforms to provide a clinically useful tool. Methods: Gas Chromatography-Mass Spectrometry (GC-TOFMS) based metabolomics and immunoassay-based protein/peptide analyses on samples from patients with PD diagnosed in Northern Sweden. Low molecular weight compounds from both plasma and cerebrospinal fluid (CSF) from 20 healthy subjects (controls) and 20 PD patients at the time of diagnosis (baseline) were analyzed. Results: In plasma, we found a significant increase in several amino acids and a decrease in C16-C18 saturated and unsaturated fatty acids in patients as compared to control subjects. We also observed an increase in plasma levels of pyroglutamate and 2-oxoisocaproate (ketoleucine) that may be indicative of increased metabolic stress in patients. In CSF, there was a generally lower level of metabolites in PD as compared to controls, with a specific decrease in 3-hydroxyisovaleric acid, tryptophan and creatinine. Multivariate analysis and modeling of metabolites indicates that while the PD samples can be separated from control samples, the list of detected compounds will need to be expanded in order to define a robust predictive model. CSF biomarker immunoassays of candidate peptide/protein biomarkers revealed a significant decrease in the levels of A beta-38 and A beta-42, and an increase in soluble APP alpha in CSF of patients. Furthermore, these peptides showed significant correlations to each other, and positive correlations to the CSF levels of several 5- and 6-carbon sugars. However, combining these metabolites and proteins/peptides into a single model did not significantly improve the statistical analysis. Conclusions: Together, this metabolomics study has detected significant alterations in plasma and CSF levels of a cluster of amino acids, fatty acids and sugars based on clinical diagnosis and levels of known protein and peptide biomarkers.
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| 5. |
- Celojevic, Dragana, 1985, et al.
(författare)
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EPHA2 polymorphisms in Estonian patients with age-related cataract.
- 2016
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Ingår i: Ophthalmic genetics. - : Informa UK Limited. - 1744-5094 .- 1381-6810. ; 37:1, s. 14-18
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background: Ephrin receptors (Ephs) are tyrosine kinases that together with their ligands, ephrins, are considered important in cell-cell communication, especially during embryogenesis but also for epithelium homeostasis. Studies have demonstrated the involvement of mutations or common variants of the gene encoding Eph receptor A2 (EPHA2), in congenital cataract and in age-related cataract. This study investigated a number of disease-associated single nucleotide polymorphisms (SNPs) in EPHA2 in patients with age-related cataract. Materials and methods: The study included 491 Estonian patients who had surgery for age-related cataract, classified as nuclear, cortical, posterior subcapsular and mixed lens opacities, and 185 controls of the same ethnical origin. Seven SNPs in EPHA2 (rs7543472, rs11260867, rs7548209, rs3768293, rs6603867, rs6678616, rs477558) were genotyped using TaqMan Allelic Discrimination. Statistical analyses for single factor associations used χ(2)-test and logistic regression was performed including relevant covariates (age, sex and smoking). Results: In single-SNP allele analysis, only the rs7543472 showed a borderline significant association with risk of cataract (p=0.048). Regression analysis with known risk factors for cataract showed no significant associations of the studied SNPs with cataract. Stratification by cataract subtype did not alter the results. Adjusted odds ratios were between 0.82 and 1.16 (95% confidence interval 0.61-1.60). Conclusions: The present study does not support a major role of EphA2 in cataractogenesis in an Estonian population.
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| 6. |
- Olsson, Bob, 1969, et al.
(författare)
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CSF and blood biomarkers for the diagnosis of Alzheimer's disease: a systematic review and meta-analysis.
- 2016
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Ingår i: The Lancet. Neurology. - 1474-4465. ; 15:7, s. 673-684
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease biomarkers are important for early diagnosis in routine clinical practice and research. Three core CSF biomarkers for the diagnosis of Alzheimer's disease (Aβ42, T-tau, and P-tau) have been assessed in numerous studies, and several other Alzheimer's disease markers are emerging in the literature. However, there have been no comprehensive meta-analyses of their diagnostic performance. We systematically reviewed the literature for 15 biomarkers in both CSF and blood to assess which of these were most altered in Alzheimer's disease.
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| 7. |
- 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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| 8. |
- 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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| 9. |
- 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 12months 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 6months 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 6months 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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| 10. |
- Jons, Daniel, 1974, et al.
(författare)
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Axonal injury in asymptomatic individuals preceding onset of multiple sclerosis
- 2022
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Ingår i: Annals of Clinical and Translational Neurology. - : Wiley. - 2328-9503. ; 9:6, s. 882-887
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Tidskriftsartikel (refereegranskat)abstract
- Axonal loss is the main cause of irreversible disability in multiple sclerosis (MS). Serum neurofilament light (sNfL) is a biomarker of axonal disintegration. In this nested case-control study, blood samples from 519 presymptomatic persons (age range 4-39 years) who later received an MS diagnosis showed higher sNfL concentrations than 519 matched controls (p < 0.0001), noticeable at least 10 years before clinical MS onset. Mean values for pre-MS and control groups were 9.6 pg/mL versus 7.4 pg/mL 0-5 years before onset, and 6.4 pg/mL versus 5.8 pg/mL 5-10 years before onset. These results support that axonal injury occurs early in MS pathogenesis.
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