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Article: Biomarkers in Neurodegenerative Diseases.

Jeromin, Andreas / Bowser, Robert

2017 Volume 15, Page(s) 491–528

Abstract: The past decade has seen tremendous efforts in biomarker discovery and validation for neurodegenerative diseases. The source and type of biomarkers has continued to grow for central nervous system diseases, from biofluid-based biomarkers (blood or ... ...

Abstract	The past decade has seen tremendous efforts in biomarker discovery and validation for neurodegenerative diseases. The source and type of biomarkers has continued to grow for central nervous system diseases, from biofluid-based biomarkers (blood or cerebrospinal fluid (CSF)), to nucleic acids, tissue, and imaging. While DNA remains a predominant biomarker used to identify familial forms of neurodegenerative diseases, various types of RNA have more recently been linked to familial and sporadic forms of neurodegenerative diseases during the past few years. Imaging approaches continue to evolve and are making major contributions to target engagement and early diagnostic biomarkers. Incorporation of biomarkers into drug development and clinical trials for neurodegenerative diseases promises to aid in the development and demonstration of target engagement and drug efficacy for neurologic disorders. This review will focus on recent advancements in developing biomarkers for clinical utility in Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS).
MeSH term(s)	Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Amyotrophic Lateral Sclerosis/diagnostic imaging ; Amyotrophic Lateral Sclerosis/genetics ; Amyotrophic Lateral Sclerosis/metabolism ; Biomarkers/blood ; Biomarkers/cerebrospinal fluid ; Biomarkers/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; DNA/genetics ; Humans ; Neurodegenerative Diseases/diagnostic imaging ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/metabolism ; Parkinson Disease/diagnostic imaging ; Parkinson Disease/genetics ; Parkinson Disease/metabolism ; Prognosis ; RNA/genetics
Chemical Substances	Biomarkers ; RNA (63231-63-0) ; DNA (9007-49-2)
Language	English
Publishing date	2017-07-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	2190-5215
ISSN	2190-5215
DOI	10.1007/978-3-319-57193-5_20
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Article: Correction: Chaby et al. Cross-Platform Evaluation of Commercially Targeted and Untargeted Metabolomics Approaches to Optimize the Investigation of Psychiatric Disease.

Chaby, Lauren E / Lasseter, Heather C / Contrepois, Kévin / Salek, Reza M / Turck, Christoph W / Thompson, Andrew / Vaughan, Timothy / Haas, Magali / Jeromin, Andreas

Metabolites

2023 Volume 13, Issue 8

Abstract: In the original publication [ ... ]. ...

Abstract	In the original publication [...].
Language	English
Publishing date	2023-08-09
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo13080933
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Article ; Online: Biomarkers of Alzheimer's disease and neurodegeneration in dried blood spots-A new collection method for remote settings.

Huber, Hanna / Blennow, Kaj / Zetterberg, Henrik / Boada, Mercé / Jeromin, Andreas / Weninger, Haley / Nuñez-Llaves, Raul / Aguilera, Núria / Ramis, Maribel / Simrén, Joel / Nilsson, Johanna / Lantero-Rodriguez, Juan / Orellana, Adelina / García-Gutiérrez, Fernando / Morató, Xavier / Ashton, Nicholas J / Montoliu-Gaya, Laia

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 4, Page(s) 2340–2352

Abstract: Background: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPS: Methods: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic ... ...

Abstract	Background: We aimed to evaluate the precision of Alzheimer's disease (AD) and neurodegeneration biomarker measurements from venous dried plasma spots (DPS Methods: In a discovery (n = 154) and a validation cohort (n = 115), glial fibrillary acidic protein (GFAP); neurofilament light (NfL); amyloid beta (Aβ) 40, Aβ42; and phosphorylated tau (p-tau181 and p-tau217) were measured in paired DPS Results: All DPS Discussion: Our data suggest that measuring blood biomarkers related to AD pathology and neurodegeneration from DPS Highlights: A wide array of biomarkers related to Alzheimer's disease (AD) and neurodegeneration were detectable in dried plasma spots (DPS
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides ; Plasma ; Amyloidogenic Proteins ; Biomarkers ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; Amyloidogenic Proteins ; Biomarkers ; tau Proteins
Language	English
Publishing date	2024-01-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13697
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Article ; Online: Cross-platform comparison of highly sensitive immunoassay technologies for cytokine markers: Platform performance in post-traumatic stress disorder and Parkinson's disease.

Lasseter, Heather C / Provost, Allison C / Chaby, Lauren E / Daskalakis, Nikolaos P / Haas, Magali / Jeromin, Andreas

Cytokine: X

2020 Volume 2, Issue 2, Page(s) 100027

Abstract: There is mounting evidence of systemic inflammation in post-traumatic stress disorder (PTSD) and Parkinson's disease (PD), yet inconsistency and a lack of replicability in findings of putative biological markers have delayed progress in this space. ... ...

Abstract	There is mounting evidence of systemic inflammation in post-traumatic stress disorder (PTSD) and Parkinson's disease (PD), yet inconsistency and a lack of replicability in findings of putative biological markers have delayed progress in this space. Variability in performance between platforms may contribute to the lack of consensus in the biomarker literature, as has been seen for a number of psychiatric disorders, including PTSD. Thus, there is a need for high-performance, scalable, and validated platforms for the discovery and development of biomarkers of inflammation for use in drug development and as clinical diagnostics. To identify the best platform for use in future biomarker discovery efforts, we conducted a comprehensive cross-platform and cross-assay evaluation across five leading platform technologies. This initial assessment focused on four cytokines that have been implicated PTSD - interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. To assess platform performance and understand likely measurements in individuals with brain disorders, serum and plasma samples were obtained from individuals with PTSD (n = 13) or Parkinson's Disease (n = 14) as well as healthy controls (n = 5). We compared platform performance across a number of common analytic parameters, including assay precision, sensitivity, frequency of endogenous analyte detection (FEAD), correlation between platforms, and parallelism in measurement of cytokines using a serial dilution series. The single molecule array (Simoa™) ultra-sensitive platform (Quanterix), MESO V-Plex (Mesoscale Discovery), and Luminex xMAP® (Myriad) were conducted by their respective vendors, while Luminex® and Quantikine® high-sensitivity ELISA assays were evaluated by R&D System's Biomarker Testing Services. The assay with the highest sensitivity in detecting endogenous analytes across all analytes and clinical populations (i.e. the highest FEAD), was the Simoa™ platform. In contrast, more variable performance was observed for MESO V-plex, R&D Luminex® and Quantikine®, while Myriad's Luminex xMAP® exhibited low FEAD across all analytes and samples. Simoa™ also demonstrated high precision in detecting endogenous cytokines, as reflected in < 20 percent coefficient of variance (%CV) across replicate runs for samples from the healthy controls, PTSD patients, and PD patients. In contrast, MESO V-Plex, R&D Luminex® and Quantikine® had variable performance in terms of precision across cytokines. Myriad Luminex xMAP® could not be included in precision estimates because the vendor did not run samples in duplicate. For cross-platform performance comparisons, the highest cross-platform correlations were observed for IL-6 such that all platforms - except for Myriad's Luminex xMAP® - had strong correlations with one another in measurements of IL-6 (r range = 0.59 - 0.86). For the other cytokines, there was low to no correlation across platforms, such that reported measurements of IL-1β, TNF-α, and IFN-γ varied across assays. Taken together, these findings provide novel evidence that the choice of immunoassay could greatly impact reported cytokine findings. The current study provides crucial information on the variability in performance between platforms and across immunoassays that may help inform the selection of assay in future research studies. Further, the results emphasize the need for performing comparative evaluations of immunoassays as new technologies emerge over time, particularly given the lack of reference standards for the quantitative assessments of cytokines.
Language	English
Publishing date	2020-04-28
Publishing country	Netherlands
Document type	Journal Article
ISSN	2590-1532
ISSN (online)	2590-1532
DOI	10.1016/j.cytox.2020.100027
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Article ; Online: Leveling the Playing Field: A New Initiative to Publish Negative and Replication Data in Brain Trauma.

Ferland-Beckham, Chantelle / Petty, Sandra / Prager, Eric / Harmon, Nicole / Haas, Magali / Jeromin, Andreas

Neurotrauma reports

2020 Volume 1, Issue 1, Page(s) 146–147

Language	English
Publishing date	2020-10-29
Document type	Editorial
ISSN	2689-288X
ISSN (online)	2689-288X
DOI	10.1089/neur.2020.0055
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Article: Sex Differences in Circulating T-Tau Trajectories After Sports-Concussion and Correlation With Outcome.

Mondello, Stefania / Guedes, Vivian A / Lai, Chen / Jeromin, Andreas / Bazarian, Jeffrey J / Gill, Jessica M

Frontiers in neurology

2020 Volume 11, Page(s) 651

Abstract: Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological ... ...

Abstract	Sex differences in molecular biomarkers after sports-related concussion (SRC) could steadily advance our understanding of injury heterogeneity and complexity, and help capture phenotypic characteristics, by unveiling sex-dependent pathobiological processes and disease mechanisms. Such knowledge will help improve diagnosis, clinical management, and prognosis. Total-tau (t-tau) has recently emerged as a promising blood marker showing sex-associated differences in neurodegenerative diseases. Nonetheless, to date, little is known about the potential influence of sex on its injury-related concentration and dynamics after SRC. We hypothesized that measurements of circulating levels of t-tau over time would reflect a differential vulnerability signature, providing insights into the sex-related phenotypes and their relationship with clinical outcomes. To test this hypothesis, plasma levels of t-tau were measured using an ultrasensitive immunoassay up to 7 days after injury, in 46 concussed athletes (20 males, 26 females). We used trajectory analysis to generate two distinct temporal profiles of t-tau, which were then compared with gender and return to play (RTP). The majority of subjects (~63%) started with low t-tau concentrations that further declined within the first 48 h; while the remaining ("maximal decliners") started with concentrations comparable to the baseline levels that also fell over time, but persisting markedly higher compared with the first profile. The maximal decliner group was primarily composed of female subjects (
Language	English
Publishing date	2020-07-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2020.00651
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Article ; Online: Assessing the commutability of candidate reference materials for the harmonization of neurofilament light measurements in blood.

Andreasson, Ulf / Gobom, Johan / Delatour, Vincent / Auclair, Guy / Noam, Yoav / Lee, Stephen / Wen, Jason / Jeromin, Andreas / Arslan, Burak / Maceski, Aleksandra / Willemse, Eline / Zetterberg, Henrik / Kuhle, Jens / Blennow, Kaj

Clinical chemistry and laboratory medicine

2023 Volume 61, Issue 7, Page(s) 1245–1254

Abstract: Objectives: Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for ... ...

Abstract	Objectives: Neurofilament light chain (NfL) concentration in blood is a biomarker of neuro-axonal injury in the nervous system and there now exist several assays with high enough sensitivity to measure NfL in serum and plasma. There is a need for harmonization with the goal of creating a certified reference material (CRM) for NfL and an early step in such an effort is to determine the best matrix for the CRM. This is done in a commutability study and here the results of the first one for NfL in blood is presented. Methods: Forty paired individual serum and plasma samples were analyzed for NfL on four different analytical platforms. Neat and differently spiked serum and plasma were evaluated for their suitability as a CRM using the difference in bias approach. Results: The correlation between the different platforms with regards to measured NfL concentrations were very high (Spearman's ρ≥0.96). Samples spiked with cerebrospinal fluid (CSF) showed higher commutability compared to samples spiked with recombinant human NfL protein and serum seems to be a better choice than plasma as the matrix for a CRM. Conclusions: The results from this first commutability study on NfL in serum/plasma showed that it is feasible to create a CRM for NfL in blood and that spiking should be done using CSF rather than with recombinant human NfL protein.
MeSH term(s)	Humans ; Intermediate Filaments ; Neurofilament Proteins ; Serum ; Plasma ; Reference Standards ; Biomarkers ; Recombinant Proteins
Chemical Substances	Neurofilament Proteins ; Biomarkers ; Recombinant Proteins
Language	English
Publishing date	2023-01-31
Publishing country	Germany
Document type	Journal Article
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2022-1181
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Article: Cross-Platform Evaluation of Commercially Targeted and Untargeted Metabolomics Approaches to Optimize the Investigation of Psychiatric Disease.

Chaby, Lauren E / Lasseter, Heather C / Contrepois, Kévin / Salek, Reza M / Turck, Christoph W / Thompson, Andrew / Vaughan, Timothy / Haas, Magali / Jeromin, Andreas

Metabolites

2021 Volume 11, Issue 9

Abstract: Metabolomics methods often encounter trade-offs between quantification accuracy and coverage, with truly comprehensive coverage only attainable through a multitude of complementary assays. Due to the lack of standardization and the variety of ... ...

Abstract	Metabolomics methods often encounter trade-offs between quantification accuracy and coverage, with truly comprehensive coverage only attainable through a multitude of complementary assays. Due to the lack of standardization and the variety of metabolomics assays, it is difficult to integrate datasets across studies or assays. To inform metabolomics platform selection, with a focus on posttraumatic stress disorder (PTSD), we review platform use and sample sizes in psychiatric metabolomics studies and then evaluate five prominent metabolomics platforms for coverage and performance, including intra-/inter-assay precision, accuracy, and linearity. We found performance was variable between metabolite classes, but comparable across targeted and untargeted approaches. Within all platforms, precision and accuracy were highly variable across classes, ranging from 0.9-63.2% (coefficient of variation) and 0.6-99.1% for accuracy to reference plasma. Several classes had high inter-assay variance, potentially impeding dissociation of a biological signal, including glycerophospholipids, organooxygen compounds, and fatty acids. Coverage was platform-specific and ranged from 16-70% of PTSD-associated metabolites. Non-overlapping coverage is challenging; however, benefits of applying multiple metabolomics technologies must be weighed against cost, biospecimen availability, platform-specific normative levels, and challenges in merging datasets. Our findings and open-access cross-platform dataset can inform platform selection and dataset integration based on platform-specific coverage breadth/overlap and metabolite-specific performance.
Language	English
Publishing date	2021-09-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662251-8
ISSN	2218-1989
ISSN	2218-1989
DOI	10.3390/metabo11090609
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Article ; Online: Membrane binding of Neuronal Calcium Sensor-1 (NCS1).

Lemire, Samuel / Jeromin, Andreas / Boisselier, Élodie

Colloids and surfaces. B, Biointerfaces

2016 Volume 139, Page(s) 138–147

Abstract: Neuronal Calcium Sensor-1 (NCS1) belongs to the family of Neuronal Calcium Sensor (NCS) proteins. NCS1 is composed of four EF-hand motifs and an N-terminal myristoylation. However, the presence of a calcium-myristoyl switch in NCS1 and its role in the ... ...

Abstract	Neuronal Calcium Sensor-1 (NCS1) belongs to the family of Neuronal Calcium Sensor (NCS) proteins. NCS1 is composed of four EF-hand motifs and an N-terminal myristoylation. However, the presence of a calcium-myristoyl switch in NCS1 and its role in the membrane binding are controversial. The model of Langmuir lipid monolayers is thus used to mimic the cell membrane in order to characterize the membrane interactions of NCS1. Two binding parameters are calculated from monolayer measurements: the maximum insertion pressure, up to which protein binding is energetically favorable, and the synergy, reporting attractive or repulsive interactions with the lipid monolayers. Binding membrane measurements performed in the presence of myristoylated NCS1 reveal better binding interactions for phospholipids composed of phosphoethanolamine polar head groups and unsaturated fatty acyl chains. In the absence of calcium, the membrane binding measurements are drastically modified and suggest that the protein is more strongly bound to the membrane. Indeed, the binding of calcium by three EF-hand motifs of NCS1 leads to a conformation change. NCS1 arrangement at the membrane could thus be reshuffled for better interactions with its substrates. The N-terminal peptide of NCS1 is composed of two amphiphilic helices involved in the membrane interactions of NCS1. Moreover, the presence of the myristoyl group has a weak influence on the membrane binding of NCS1 suggesting the absence of a calcium-myristoyl switch mechanism in this protein. The myristoylation could thus have a structural role required in the folding/unfolding of NCS1 which is essential to its multiple biological functions.
MeSH term(s)	Amino Acid Sequence ; Calcium/metabolism ; Calcium-Binding Proteins/chemistry ; Calcium-Binding Proteins/metabolism ; Cell Membrane/chemistry ; Cell Membrane/metabolism ; Ethanolamines/chemistry ; Humans ; Models, Molecular ; Molecular Sequence Data ; Myristic Acid/metabolism ; Neuronal Calcium-Sensor Proteins/chemistry ; Neuronal Calcium-Sensor Proteins/metabolism ; Neuropeptides/chemistry ; Neuropeptides/metabolism ; Phospholipids/chemistry ; Protein Binding ; Protein Processing, Post-Translational ; Protein Structure, Secondary ; Recombinant Proteins/chemistry ; Recombinant Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/chemistry ; Saccharomyces cerevisiae Proteins/metabolism ; Schizosaccharomyces/metabolism ; Sequence Alignment ; Sequence Homology, Amino Acid
Chemical Substances	Calcium-Binding Proteins ; Ethanolamines ; FRQ1 protein, S cerevisiae ; Neuronal Calcium-Sensor Proteins ; Neuropeptides ; Phospholipids ; Recombinant Proteins ; Saccharomyces cerevisiae Proteins ; frequenin calcium sensor proteins ; Myristic Acid (0I3V7S25AW) ; phosphorylethanolamine (78A2BX7AEU) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2016-03-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2015.11.065
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Article ; Online: Analytical performance of a CE-marked immunoassay to quantify phosphorylated neurofilament heavy chains.

De Schaepdryver, Maxim / Goossens, Janne / Jeromin, Andreas / Brix, Britta / Van Damme, Philip / Poesen, Koen

Clinical chemistry and laboratory medicine

2019 Volume 57, Issue 8, Page(s) e199–e202

MeSH term(s)	Amyotrophic Lateral Sclerosis/cerebrospinal fluid ; Amyotrophic Lateral Sclerosis/diagnosis ; Biomarkers/analysis ; Cerebrospinal Fluid/chemistry ; Enzyme-Linked Immunosorbent Assay ; Humans ; Neurofilament Proteins/analysis ; Phosphorylation
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2019-02-01
Publishing country	Germany
Document type	Letter
ZDB-ID	1418007-8
ISSN	1437-4331 ; 1434-6621 ; 1437-8523
ISSN (online)	1437-4331
ISSN	1434-6621 ; 1437-8523
DOI	10.1515/cclm-2018-1004
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