| 161. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Discriminatory analysis of biochip-derived protein patterns in CSF and plasma in neurodegenerative diseases
- 2011
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Ingår i: Frontiers in Aging Neuroscience. - : Frontiers Media SA. - 1663-4365. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The role of biomarkers in neurodegenerative diseases has been emphasized by recent research. Future clinical demands for identifying diseases at an early stage may render them essential. The aim of this pilot study was to test the analytical performance of two multiplex assays of cerebral markers on a well-defined clinical material consisting of patients with various neurodegenerative diseases. We measured 10 analytes in plasma and cerebrospinal fluid (CSF) from 60 patients suffering from Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, dementia with Lewy bodies, or mild cognitive impairment, as well as 20 cognitively healthy controls. We used the Randox biochip-based Evidence Investigator™ system to measure the analytes. We found it possible to measure most analytes in both plasma and CSF, and there were some interesting differences between the diagnostic groups, although with large overlaps. CSF heart-type fatty acid-binding protein was increased in AD. Glial fibrillary acidic protein and neutrophil gelatinase-associated lipocalin in CSF and D-dimer in plasma were elevated in patients with cerebrovascular disease. A multivariate statistical analysis revealed that the pattern of analytes could help to differentiate the conditions, although more studies are required to verify this.
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| 162. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Increased Levels of Chitotriosidase and YKL-40 in Cerebrospinal Fluid from Patients with Alzheimer's Disease.
- 2014
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Ingår i: Dementia and geriatric cognitive disorders extra. - : S. Karger AG. - 1664-5464. ; 4:2, s. 297-304
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Tidskriftsartikel (refereegranskat)abstract
- The cerebrospinal fluid (CSF) biomarkers total tau, abnormally phosphorylated tau and amyloid β 1-42 are strongly associated with Alzheimer's disease (AD). Apart from the pathologic hallmarks that these biomarkers represent, other processes such as inflammation and microglial activation are present in the brains of patients with AD. New biomarkers related to these processes could be valuable for the diagnosis and follow-up of AD patients and for the evaluation of inflammation-related pathologies.
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| 163. |
- Roughton, Karolina, 1977, et al.
(författare)
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Lipopolysaccharide-Induced Inflammation Aggravates Irradiation-Induced Injury to the Young Mouse Brain.
- 2013
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Ingår i: Developmental neuroscience. - : S. Karger AG. - 1421-9859 .- 0378-5866. ; 35:5, s. 406-415
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Tidskriftsartikel (refereegranskat)abstract
- Radiotherapy is an effective treatment strategy in the treatment of brain tumors, but it is also a major cause of long-term complications, especially in survivors of pediatric brain tumors. Cognitive decline caused by cranial radiotherapy is thought, at least partly, to depend on injury to stem and progenitor cells in the dentate gyrus of the hippocampus. This study investigated the effects of lipopolysaccharide (LPS)-induced inflammation at the time of irradiation (IR) in the growing mouse brain. A single injection of LPS (0.3 mg/kg) was administered 24 h prior to cranial IR of 14-day-old male mice. LPS pretreatment increased the levels of the chemokine CCL2 and the cytokine IL-1β in the brain by 440 and 560%, respectively, compared to IR alone. IR disrupted hippocampal neurogenesis and the growth of the dentate gyrus, and the mice pretreated with LPS displayed an even more pronounced lack of growth than the vehicle-treated group 2 months after IR. The density of microglia was not affected, but LPS-pretreated mice displayed 48% fewer bromodeoxyuridine-positive cells and 43% fewer doublecortin-positive cells in the granule cell layer 2 months after IR compared with the vehicle-treated group. In conclusion, an ongoing inflammation in the brain at the time of IR further enhanced the IR-induced loss of neurogenesis, and may aggravate future cognitive deficits in patients treated with cranial radiotherapy.
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| 164. |
- Shahim, Pashtun, 1984, et al.
(författare)
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Serum neurofilament light protein predicts clinical outcome in traumatic brain injury
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Axonal white matter injury is believed to be a major determinant of adverse outcomes following traumatic brain injury (TBI). We hypothesized that measurement of neurofilament light protein (NF-L), a protein found in long white-matter axons, in blood samples, may serve as a suitable biomarker for neuronal damage in TBI patients. To test our hypotheses, we designed a study in two parts: i) we developed an immunoassay based on Single molecule array technology for quantification of NF-L in blood, and ii) in a proof-of-concept study, we tested our newly developed method on serial serum samples from severe TBI (sTBI) patients (n = 72) and controls (n = 35). We also compared the diagnostic and prognostic utility of NF-L with the established blood biomarker S100B. NF-L levels were markedly increased in sTBI patients compared with controls. NF-L at admission yielded an AUC of 0.99 to detect TBI versus controls (AUC 0.96 for S100B), and increased to 1.00 at day 12 (0.65 for S100B). Importantly, initial NF-L levels predicted poor 12-month clinical outcome. In contrast, S100B was not related to outcome. Taken together, our data suggests that measurement of serum NF-L may be useful to assess the severity of neuronal injury following sTBI.
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| 165. |
- Simrén, Joel, 1996, et al.
(författare)
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Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5-90 years
- 2022
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Ingår i: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 4:4
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Tidskriftsartikel (refereegranskat)abstract
- The recent development of assays that accurately quantify neurofilament light, a neuronal cytoskeleton protein, in plasma has generated a vast literature supporting that it is a sensitive, dynamic, and robust biomarker of neuroaxonal damage. As a result, efforts are now made to introduce plasma neurofilament light into clinical routine practice, making it an easily accessible complement to its cerebrospinal fluid counterpart. An increasing literature supports the use of plasma neurofilament light in differentiating neurodegenerative diseases from their non-neurodegenerative mimics and suggests it is a valuable biomarker for the evaluation of the effect of putative disease-modifying treatments (e.g. in multiple sclerosis). More contexts of use will likely emerge over the coming years. However, to assist clinical interpretation of laboratory test values, it is crucial to establish normal reference intervals. In this study, we sought to derive reliable cut-offs by pooling quantified plasma neurofilament light in neurologically healthy participants (5-90 years) from eight cohorts. A strong relationship between age and plasma neurofilament light prompted us to define the following age-partitioned reference limits (upper 95(th) percentile in each age category): 5-17 years = 7 pg/mL; 18-50 years = 10 pg/mL; 51-60 years = 15 pg/mL; 61-70 years = 20 pg/mL; 70 + years = 35 pg/mL. The established reference limits across the lifespan will aid the introduction of plasma neurofilament light into clinical routine, and thereby contribute to diagnostics and disease-monitoring in neurological practice. Simren et al. report age-stratified cut-offs for plasma neurofilament light, based on a large material of healthy individuals across the ages 5-90 years. The findings will assist clinical implementation of plasma neurofilament light in clinical routine, by simplifying interpretation of concentrations across the lifespan as neurofilament light increases with age.
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| 166. |
- Sjölander, Annica, 1969, et al.
(författare)
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BACE1 gene variants do not influence BACE1 activity, levels of APP or Abeta isoforms in CSF in Alzheimer's disease.
- 2010
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Ingår i: Molecular neurodegeneration. - : Springer Science and Business Media LLC. - 1750-1326. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: The BACE1 gene encodes the beta-site APP-cleaving enzyme 1 and has been associated with Alzheimer's disease (AD). BACE1 is the most important beta-secretase responsible for the generation of Alzheimer-associated amyloid beta-proteins (Abeta) and may play a role in the amyloidogenic process in AD. We hypothesized that BACE1 gene variants might influence BACE1 activity or other markers for APP metabolism in the cerebrospinal fluid (CSF) and thereby contribute to the development of AD. We genotyped a Swedish sample of 269 AD patients for the rs638405 single nucleotide polymorphism (SNP) in the BACE1 gene and correlated genotype data to a broad range of amyloid-related biomarkers in CSF, including BACE1 activity, levels of Abeta40, Abeta42, alpha- and beta-cleaved soluble APP (alpha-sAPP and beta-sAPP), as well as markers for Alzheimer-type axonal degeneration, i.e., total-tau and phospho-tau181. Gene variants of BACE1 were neither associated with amyloid-related biomarkers, nor with markers for axonal degeneration in AD.
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| 167. |
- Slemmon, J Randall, et al.
(författare)
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Measurement of Aβ1-42 in cerebrospinal fluid is influenced by matrix effects.
- 2012
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Ingår i: Journal of neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 120:2, s. 325-33
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Tidskriftsartikel (refereegranskat)abstract
- Aβ1-42 measurement in CSF is an important biochemical marker for Alzheimer disease (AD). However, our understanding of why this biomarker is predictive and why it is often difficult to measure in a reproducible fashion is still lacking. To study these questions, the concentration of Aβ1-42 in CSF was compared before and after denaturation with 6M guanidine and reverse-phase HPLC. Measurement of the Aβ1-42 after denaturation and reverse-phase HPLC demonstrated that considerably more Aβ1-42 was present in CSF than revealed when assaying non-denatured CSF. A comparison of Aβ1-42 concentrations before and after HPLC in AD CSF with that in normal controls suggested that matrix interference may affect the differentiation between the diagnostic groups. A similar effect was observed with dilutions of crude CSF. Together, these results suggested that at least part of the mechanism by which low Aβ1-42 concentrations in CSF function as a biomarker of AD is related to matrix components which preferentially hide a portion of the Aβ1-42 from detection in AD CSF. In contrast, we show that the association of the APOEε4 allele with lower Aβ1-42 concentrations in CSF is preserved even after denaturation and HPLC. A similar relationship between the presence of the APOEε4 allele and lower concentrations of Aβ1-40 was also apparent, thereby generating similar ratios of Aβ1-42/ Aβ1-40 across the APOE genotypes. The results from the present study suggested that Aβ1-42 in CSF functions as a biomarker of AD in tandem with other CSF matrix components that are increased in AD CSF. Further studies are needed to identify which matrix factors (e.g. binding of Aβ to proteins) underlie the increased detection of Aβ1-42 concentrations after denaturation and HPLC. The data also suggested that denaturation and HPLC of CSF may be a useful approach for studies using Aβ1-42 as a pharmacodynamic marker or in other paradigms where measurement of total non-covalently bound Aβ1-42 is required.
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| 168. |
- Smith, Rebecca G., et al.
(författare)
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Blood DNA methylomic signatures associated with CSF biomarkers of Alzheimer's disease in the EMIF-AD study
- 2024
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Ingår i: Alzheimer's & Dementia. - : John Wiley & Sons. - 1552-5260 .- 1552-5279.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: We investigated blood DNA methylation patterns associated with 15 well-established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration.METHODS: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF-AD) study using the EPIC array.RESULTS: We identified Bonferroni-significant differential methylation associated with CSF YKL-40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL-40 levels correlating with plasma YKL-40 levels. A co-localization analysis showed shared genetic variants underlying YKL-40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co-methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development.DISCUSSION: We conducted the most comprehensive epigenome-wide association study (EWAS) of AD-relevant CSF biomarkers to date. Future work should explore the relationship between YKL-40 genotype, DNA methylation, and protein levels in the brain.HIGHLIGHTS: Blood DNA methylation was assessed in the EMIF-AD MBD study. Epigenome-wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)-relevant cerebrospinal fluid (CSF) biomarker measures. Five Bonferroni-significant loci were associated with YKL-40 levels and seven with neurofilament light chain (NfL). DNA methylation in YKL-40 co-localized with previously reported genetic variation. DNA methylation potentially mediates the effect of single-nucleotide polymorphisms (SNPs) in YKL-40 on CSF protein levels.
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| 169. |
- Stanne, Tara M, 1979, et al.
(författare)
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Low Circulating Acute Brain-Derived Neurotrophic Factor Levels Are Associated With Poor Long-Term Functional Outcome After Ischemic Stroke.
- 2016
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Ingår i: Stroke; a journal of cerebral circulation. - 1524-4628 .- 0039-2499. ; 47:7, s. 1943-1945
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Tidskriftsartikel (refereegranskat)abstract
- Brain-derived neurotrophic factor (BDNF) plays important roles in brain plasticity and repair, and it influences stroke outcomes in animal models. Circulating BDNF concentrations are lowered in patients with traumatic brain injury, and low BDNF predicts poor recovery after this injury. We sought to investigate whether circulating concentrations of BDNF are altered in the acute phase of ischemic stroke and whether they are associated with short- or long-term functional outcome.
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| 170. |
- Van Hulle, Carol, et al.
(författare)
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An examination of a novel multipanel of CSF biomarkers in the Alzheimer's disease clinical and pathological continuum.
- 2021
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Ingår i: Alzheimer's & dementia : the journal of the Alzheimer's Association. - : Wiley. - 1552-5279. ; 17:3, s. 431-445
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Tidskriftsartikel (refereegranskat)abstract
- This study examines the utility of a multipanel of cerebrospinal fluid (CSF) biomarkers complementing Alzheimer's disease (AD) biomarkers in a clinical research sample. We compared biomarkers across groups defined by clinical diagnosis and pTau181 /Aβ42 status (+/-) and explored their value in predicting cognition.CSF biomarkers amyloid beta (Aβ)42 , pTau181 , tTau, Aβ40 , neurogranin, neurofilament light (NfL), α-synuclein, glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL-40), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), S100 calcium binding protein B (S100B), and interleukin 6 (IL6), were measured with the NeuroToolKit (NTK) for 720 adults ages 40 to 93 years (mean age=63.9 years, standard deviation [SD]=9.0; 50 with dementia; 54 with mild cognitive impairment [MCI], 616 unimpaired).Neurodegeneration and glial activation biomarkers were elevated in pTau181 /Aβ42 + MCI/dementia participants relative to all pTau181 /Aβ42 - participants. Neurodegeneration biomarkers increased with clinical severity among pTau181 /Aβ42 + participants and predicted worse cognitive performance. Glial activation biomarkers were unrelated to cognitive performance.The NTK contains promising markers that improve the pathophysiological characterization of AD. Neurodegeneration biomarkers beyond tTau improved statistical prediction of cognition and disease stages.
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