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Sökning: WFRF:(Blennow Kaj 1958) > Uppsala universitet

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1.
  • Andersson, Malin E, 1978, et al. (författare)
  • Signs of neuroaxonal injury in preeclampsia-A case control study.
  • 2021
  • Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 16:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma.CSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum.Women with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy.NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.
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2.
  • Benedict, Christian, Docent, 1976-, et al. (författare)
  • Effects of acute sleep loss on diurnal plasma dynamics of CNS health biomarkers in young men
  • 2020
  • Ingår i: Neurology. - : LIPPINCOTT WILLIAMS & WILKINS. - 0028-3878 .- 1526-632X. ; 94:11, s. E1181-E1189
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: Disrupted sleep increases CSF levels of tau and beta -amyloid (A beta) and is associated with an increased risk of Alzheimer disease (AD). Our aim was to determine whether acute sleep loss alters diurnal profiles of plasma-based AD-associated biomarkers.Methods: In a 2-condition crossover study, 15 healthy young men participated in 2 standardized sedentary in-laboratory conditions in randomized order: normal sleep vs overnight sleep loss. Plasma levels of total tau (t-tau), A beta 40, A beta 42, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using ultrasensitive single molecule array assays or ELISAs, in the fasted state in the evening prior to, and in the morning after, each intervention.Results: In response to sleep loss (+17.2%), compared with normal sleep (+1.8%), the evening to morning ratio was increased for t-tau (p = 0.035). No changes between the sleep conditions were seen for levels of A beta 40, A beta 42, NfL, or GFAP (all p > 0.10). The AD risk genotype rs4420638 did not significantly interact with sleep loss-related diurnal changes in plasma levels of A beta 40 or A beta 42 (p > 0.10). Plasma levels of A beta 42 (-17.1%) and GFAP (-12.1%) exhibited an evening to morning decrease across conditions (p < 0.05).Conclusions: Our exploratory study suggests that acute sleep loss results in increased blood levels of t-tau. These changes provide further evidence that sleep loss may have detrimental effects on brain health even in younger individuals. Larger cohorts are warranted to delineate sleep vs circadian mechanisms, implications for long-term recurrent conditions (e.g., in shift workers), as well as interactions with other lifestyle and genetic factors.
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3.
  • Bergman, Lina, 1982, et al. (författare)
  • Blood-based cerebral biomarkers in preeclampsia: Plasma concentrations of NfL, tau, S100B and NSE during pregnancy in women who later develop preeclampsia - A nested case control study
  • 2018
  • Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:5
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective To evaluate if concentrations of the neuronal proteins neurofilament light chain and tau are changed in women developing preeclampsia and to evaluate the ability of a combination of neurofilament light chain, tau, S100B and neuron specific enolase in identifying neurologic impairment before diagnosis of preeclampsia. A nested case-control study within a longitudinal study cohort was performed. 469 healthy pregnant women were enrolled between 2004-2007 and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Plasma concentrations of tau and neurofilament light chain were analyzed in 16 women who eventually developed preeclampsia and 36 controls throughout pregnancy with single molecule array (Simoa) method and compared within and between groups. S100B and NSE had been analyzed previously in the same study population. A statistical model with receiving characteristic operation curve was constructed with the four biomarkers combined. Plasma concentrations of neurofilament light chain were significantly increased in women who developed preeclampsia in gestational week 33 (11.85 ng/L, IQR 7.48-39.93 vs 6.80 ng/L, IQR 5.65-11.40) and 37 (22.15 ng/L, IQR 10.93-35.30 vs 8.40 ng/L, IQR 6.40-14.30) and for tau in gestational week 37 (4.33 ng/L, IQR 3.97-12.83 vs 3.77 ng/L, IQR 1.91-5.25) in contrast to healthy controls. A combined model for preeclampsia with tau, neurofilament light chain, S100B and neuron specific enolase in gestational week 25 displayed an area under the curve of 0.77, in week 28 it was 0.75, in week 33 it was 0.89 and in week 37 it was 0.83. Median week for diagnosis of preeclampsia was at 38 weeks of gestation. Concentrations of both tau and neurofilament light chain are increased in the end of pregnancy in women developing preeclampsia in contrast to healthy pregnancies. Cerebral biomarkers might reflect cerebral involvement before onset of disease.
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4.
  • Bergman, Lina, 1982, et al. (författare)
  • Evidence of neuroinflammation and blood–brain barrier disruption in women with preeclampsia and eclampsia
  • 2021
  • Ingår i: Cells. - : MDPI AG. - 2073-4409. ; 10:11
  • Tidskriftsartikel (refereegranskat)abstract
    • Cerebral complications in preeclampsia are leading causes of maternal mortality. Animal models suggest that an injured blood–brain barrier and neuroinflammation may be important but there is paucity of data from human studies. Therefore, we aimed to evaluate this in women with preeclampsia and eclampsia. We included women recruited to the South African Preeclampsia Obstetric Adverse Events (PROVE) biobank. Blood and cerebrospinal fluid (CSF) were collected around delivery. CSF was analyzed for neuroinflammatory markers interleukin 1β, interleukin 6, interleukin-8 and tumor necrosis factor alpha (TNF-alpha). The CSF to plasma albumin ratio was measured to assess blood–brain barrier function. Women with eclampsia (n = 4) showed increased CSF concentrations of all pro-inflammatory cytokines and TNF-alpha compared to women with normotensive pregnancies (n = 7) and also for interleukin-6 and TNF-alpha compared to women with preeclampsia (n = 4). Women with preeclampsia also showed increases in pro-inflammatory cytokines IL-6 and IL-8 but not TNF-alpha in the CSF compared to women with normotensive pregnancies. In particular, women with eclampsia but also women with preeclampsia showed an increase in the CSF to plasma albumin ratio compared to normotensive women. In conclusion, women with preeclampsia and eclampsia show evidence of neuroinflammation and an injured blood–brain barrier. These findings are seen in particular among women with eclampsia.
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5.
  • Blennow, Kaj, 1958, et al. (författare)
  • Longitudinal stability of CSF biomarkers in Alzheimer's disease
  • 2007
  • Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 419:1, s. 18-22
  • Tidskriftsartikel (refereegranskat)abstract
    • Biomarker levels in cerebrospinal fluid (CSF) may serve as surrogate markers for treatment efficacy in clinical trials of disease-modifying drugs against Alzheimer's disease (AD). A prerequisite, however, is that the marker is sufficiently stable over time in individual patients. Here, we tested the stability of the three established CSF biomarkers for AD, total tau (T-tau), tau phosphorylated at threonine 181 (P-tau181) and the 42 amino acid isoform of β-amyloid (Aβ42), over 6 months in a cohort of AD patients on stable treatment with acetylcholinesterase (AChE) inhibitors. Fifty-three patients completed the study, 29 men and 24 women, mean age (±S.D.) 76.1 ± 7.9 years. Mean levels of CSF biomarkers were very stable between baseline and endpoint, with coefficients of variation (CVs) of 4.4–6.1%. Intra-individual biomarker levels at baseline and endpoint were also highly correlated with Pearson r-values above 0.95 (p < 0.0001), for all three markers. We conclude that T-tau, P-tau and Aβ42 concentrations in CSF are remarkably stable over a 6-month period in individual AD patients. This suggest that these biomarkers may have a potential to identify and monitor very minor biochemical changes induced by treatment, and thus support their possible usefulness as surrogate markers in clinical trials with drug candidates with disease-modifying potential, such as secretase inhibitors, Aβ immunotherapy and tau phosphorylation inhibitors.
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6.
  • Blom, Elin S., et al. (författare)
  • Rapid progression from mild cognitive impairment to Alzheimer's disease in subjects with elevated levels of tau in cerebrospinal fluid and the APOE epsilon4/epsilon4 genotype.
  • 2009
  • Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 27:5, s. 458-64
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND/AIMS: Increased cerebrospinal fluid (CSF) tau, decreased CSF amyloid-beta42 (Abeta42) and the apolipoprotein E gene (APOE) epsilon4 allele predict progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). Here, we investigated these markers to assess their predictive value and influence on the rate of disease progression. METHODS: Using ELISA, we measured the CSF biomarkers in 47 AD patients, 58 patients with MCI and 35 healthy control subjects. Twenty-eight MCI patients revisited the clinic and half of them progressed to AD during a period of 3-12 years. RESULTS: The expected changes in CSF total (T)-tau, phosphorylated (P)-tau and Abeta42 levels were found in AD, confirming the diagnostic value of these biomarkers. We were also able to corroborate an increased risk for progression from MCI to AD with elevated CSF T-tau and P-tau and with the presence of the APOE epsilon4/epsilon4 genotype, but not with decreased Abeta42. Finally, for the first time we demonstrated that MCI subjects with high CSF T-tau or P-tau and APOE epsilon4 homozygosity progressed faster from MCI to AD. CONCLUSIONS: CSF T-tau and P-tau as well as the APOE epsilon4/epsilon4 genotype are robust predictors of AD and are also associated with a more rapid progression from MCI to AD.
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7.
  • Bokström-Res, Emma, et al. (författare)
  • Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with pre-eclampsia and eclampsia
  • 2023
  • Ingår i: Pregnancy Hypertension. - : Elsevier. - 2210-7789 .- 2210-7797. ; 31, s. 38-45
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: The cerebral injury biomarkers neurofilament light chain (NfL) and tau and the glial activation biomarker glial fibrillary acidic protein (GFAP) may reflect neurological injury in pre-eclampsia. We assessed if there was a correlation between cognitive function assessment scores and plasma concentrations of these biomarkers in pre-eclampsia.Study design: Women with eclampsia, pre-eclampsia and normotensive pregnancies from the South African PROVE biobank were included. Blood samples were taken at inclusion. The Montreal Cognitive Assessment was performed after delivery at the time of discharge. The correlation between cognitive assessment scores and plasma concentrations of cerebral biomarkers was analysed using Spearman correlation adjusted for time from eclamptic seizure.Main outcome measures: We included 49 women with eclampsia, 16 women with pre-eclampsia complicated by pulmonary oedema, 22 women with pre-eclampsia without pulmonary oedema, HELLP or neurological complications and 18 women with normotensive pregnancies.Results: There was a correlation between impaired cognitive function and increased plasma concentrations of NfL in women with eclampsia and women with pre-eclampsia and pulmonary oedema (r = -0.37, p = 0.009 and r = -0.56, p = 0.025 respectively). No correlation between impaired cognitive function and NfL in pre-eclampsia cases without pulmonary oedema, HELLP or neurological complications or normotensive pregnancies was found. No correlation with cognitive impairment was found in any groups for tau or GFAP.Conclusions: We found a correlation between impaired cognitive function assessment and plasma NfL concentrations in women with eclampsia and pre-eclampsia complicated by pulmonary oedema. These findings suggest that acute neuroaxonal injury may cause or contribute to cognitive impairment in these women.
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8.
  • Braun, Madelen, et al. (författare)
  • Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus
  • 2022
  • Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 19:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Lumbar punctures are a common examination in the work-up of patients with idiopathic normal pressure hydrocephalus (iNPH) and cerebrospinal fluid (CSF) biomarkers should therefore be available for use in selection of shunt candidates. The aim of this study was to investigate if CSF biomarkers are associated with outcome after shunt surgery alone or in combination with comorbidity and imaging markers, and investigate associations between CSF biomarkers and symptoms. Methods Preoperative CSF biomarkers were analyzed in 455 patients operated with shunt surgery for iNPH at a single center during 2011-2018. Symptoms before and 12 months after shunt surgery were graded with the Swedish iNPH scale. Neurofilament light chain protein (NfL), total tau (T-tau), phosphorylated tau (P-tau) and amyloid beta1-42 (A beta 1-42) CSF levels were measured. Evans' index and disproportionately enlarged subarachnoid space hydrocephalus were measured on preoperative CT-scans. Preoperative evaluation and follow-up 12 months after shunt surgery were available in 376 patients. Results Higher levels of NfL and T-tau were associated with less improvement after shunt surgery (beta = - 3.10, p = 0.016 and beta = - 2.45, p = 0.012, respectively). Patients whose symptoms deteriorated after shunt surgery had higher preoperative levels of NfL (1250 ng/L [IQR:1020-2220] vs. 1020 [770-1649], p < 0.001) and T-tau (221 ng/L [IQR: 159-346] vs. 190 [135-261], p = 0.0039) than patients with postoperative improvement on the iNPH scale. Among the patients who improved >= 5 levels on the iNPH scale (55%), NfL was abnormal in 22%, T-tau in 14%, P-tau in 6% and A beta 1-42 in 45%, compared with normal reference limits. The inclusion of CSF biomarkers, imaging markers and comorbidity in multivariate predictive Orthogonal Projections to Latent Structures (OPLS) models to did not improve predictability in outcome after shunt surgery. Conclusions Higher levels of T-tau and NfL were associated with a less favorable response to shunt surgery, suggesting a more active neurodegeneration in this group of patients. However, CSF levels of these biomarkers can be elevated also in patients who respond to shunt surgery. Thus, none of these CSF biomarkers, alone or used in combination, are suitable for excluding patients from surgery.
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9.
  • Bridel, Claire, et al. (författare)
  • Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
  • 2019
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
  • Forskningsöversikt (refereegranskat)abstract
    • Importance  Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives  To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources  PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection  Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis  Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure  The cNfL levels adjusted for age and sex across diagnoses.Results  Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance  These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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10.
  • Burman, Joachim, et al. (författare)
  • YKL-40 is a CSF biomarker of intrathecal inflammation in secondary progressive multiple sclerosis.
  • 2016
  • Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 292, s. 52-7
  • Tidskriftsartikel (refereegranskat)abstract
    • YKL-40 (CHI3L1) is a glycoprotein predominantly produced by reactive astrocytes in chronic active MS lesions, which are common in secondary progressive MS. In this study, YKL-40 was investigated in different stages of MS and in relation to MRI findings. YKL-40 levels in CSF samples from two independent patient cohorts of MS patients were determined with ELISA. CSF YKL-40 was increased in patients with active relapsing-remitting MS and correlated with the number of gadolinium enhancing lesions. Patients with secondary progressive MS had similar high levels of YKL-40, whereas not active relapsing-remitting MS patients had YKL-40 levels comparable to healthy controls.
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