Serum GFAP and neurofilament light as biomarkers of disease activity and disability in NMOSD DOI
Mitsuru Watanabe,

Yuri Nakamura,

Zuzanna Michalak

et al.

Neurology, Journal Year: 2019, Volume and Issue: 93(13)

Published: Aug. 31, 2019

Objective

To test the hypothesis that serum levels of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), which are an intermediate astrocyte neuron filaments, respectively, clinically useful biomarkers disease activity disability in neuromyelitis optica spectrum disorders (NMOSD).

Methods

Levels GFAP NfL (sGFAP sNfL, respectively) CSF samples were measured healthy controls (HCs) (n = 49; 49 samples), patients with NMOSD 33; 42 102 multiple sclerosis (MS) 53 91 samples) by ultrasensitive single-molecule array assays. Association sGFAP sNfL clinical parameters was determined.

Results

For both NfL, strongly correlated. Both higher than HCs (both p < 0.001). Moreover, MS (median 207.7 vs 121.1 pg/mL, In NMOSD, concentration increased after recent relapse (540.9 152.9 Multivariate analyses indicated associated Expanded Disability Status Scale score (p 0.026 0.001, respectively). Higher sGFAP/sNfL quotient at differentiated from a sensitivity 73.0% specificity 75.8%.

Conclusions

likely to be good disability, is potential diagnostic marker for NMOSD.

Language: Английский

Neurofilaments as biomarkers in neurological disorders DOI
Michael Khalil, Charlotte E. Teunissen, Markus Otto

et al.

Nature Reviews Neurology, Journal Year: 2018, Volume and Issue: 14(10), P. 577 - 589

Published: Aug. 31, 2018

Language: Английский

Citations

1548
Serum Neurofilament light: A biomarker of neuronal damage in multiple sclerosis DOI Creative Commons
Giulio Disanto, Christian Barro, Pascal Benkert

et al.

Annals of Neurology, Journal Year: 2017, Volume and Issue: 81(6), P. 857 - 870

Published: May 17, 2017

Neurofilament light chains (NfL) are unique to neuronal cells, shed the cerebrospinal fluid (CSF), and detectable at low concentrations in peripheral blood. Various diseases causing damage have resulted elevated CSF concentrations. We explored value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay multiple sclerosis (MS).sNfL levels were measured healthy controls (HC, n = 254) two independent MS cohorts: (1) cross-sectional with paired samples (n 142), (2) longitudinal repeated sampling 246, median follow-up 3.1 years, interquartile range [IQR] 2.0-4.0). assessed their relation concurrent clinical, imaging, treatment parameters future clinical outcomes.sNfL higher both cohorts than HC (p < 0.001). found a strong association between sNfL (β 0.589, p Patients either brain or spinal (43.4pg/ml, IQR 25.2-65.3) gadolinium-enhancing lesions (62.5pg/ml, 42.7-71.4) had those without (29.6pg/ml, 20.9-41.8; β 1.461, 0.005 1.902, 0.002, respectively). was independently associated Expanded Disability Status Scale (EDSS) assessments 1.105, 0.001) presence relapses 1.430, lower under disease-modifying 0.818, 0.003). above 80th, 90th, 95th, 97.5th, 99th HC-based percentiles risk (97.5th percentile: incidence rate ratio 1.94, 95% confidence interval [CI] 1.21-3.10, 0.006) EDSS worsening OR 2.41, CI 1.07-5.42, 0.034).These results support as sensitive clinically meaningful blood biomarker monitor tissue effects therapies MS. Ann Neurol 2017;81:857-870.

Language: Английский

Citations

944
Association of Plasma Neurofilament Light With Neurodegeneration in Patients With Alzheimer Disease DOI
Niklas Mattsson, Ulf Andréasson, Henrik Zetterberg

et al.

JAMA Neurology, Journal Year: 2017, Volume and Issue: 74(5), P. 557 - 557

Published: March 28, 2017

Existing cerebrospinal fluid (CSF) or imaging (tau positron emission tomography) biomarkers for Alzheimer disease (AD) are invasive expensive. Biomarkers based on standard blood test results would be useful in research, drug development, and clinical practice. Plasma neurofilament light (NFL) has recently been proposed as a blood-based biomarker neurodegeneration dementias.To whether plasma NFL concentrations increased AD associated with cognitive decline, other biomarkers, evidence of neurodegeneration.In this prospective case-control study, an ultrasensitive assay was used to measure concentration 193 cognitively healthy controls, 197 patients mild impairment (MCI), 180 dementia from the Alzheimer's Disease Neuroimaging Initiative. The study dates were September 7, 2005, February 13, 2012. analysis performed 2016.Associations tested between diagnosis, Aβ pathologic features, CSF neuronal injury, cognition, brain structure, metabolism.Among impairment, dementia, correlated (Spearman ρ = 0.59, P < .001). MCI (mean, 42.8 ng/L) 51.0 compared controls 34.7 (P .001) had high diagnostic accuracy vs (area under receiver operating characteristic curve, 0.87, which is comparable established biomarkers). particularly features. High poor cognition AD-related atrophy (at baseline longitudinally) hypometabolism (longitudinally).Plasma diagnosis cognitive, biochemical, hallmarks disease. This finding implies potential usefulness noninvasive AD.

Language: Английский

Citations

817
Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer’s disease DOI

Oliver Preische,

Stephanie A. Schultz,

Anja Apel

et al.

Nature Medicine, Journal Year: 2019, Volume and Issue: 25(2), P. 277 - 283

Published: Jan. 21, 2019

Language: Английский

Citations

770
Diagnostic value of plasma phosphorylated tau181 in Alzheimer’s disease and frontotemporal lobar degeneration DOI
Elisabeth H. Thijssen, Renaud La Joie,

Amy Wolf

et al.

Nature Medicine, Journal Year: 2020, Volume and Issue: 26(3), P. 387 - 397

Published: March 1, 2020

Language: Английский

Citations

627
Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis DOI Open Access
Christian Barro, Pascal Benkert, Giulio Disanto

et al.

Brain, Journal Year: 2018, Volume and Issue: 141(8), P. 2382 - 2391

Published: May 13, 2018

Neuro-axonal injury is a key factor in the development of permanent disability multiple sclerosis. Neurofilament light chain peripheral blood has recently emerged as biofluid marker reflecting neuro-axonal damage this disease. We aimed at comparing serum neurofilament levels sclerosis and healthy controls, to determine their association with measures disease activity ability predict future clinical worsening well brain spinal cord volume loss. was measured by single molecule array assay 2183 samples collected part an ongoing cohort study from 259 patients (189 relapsing 70 progressive) control subjects. Clinical assessment, sampling MRI were done annually; median follow-up time 6.5 years. Brain volumes quantified structural image evaluation using normalization atrophy, cross-sectional, cervical analyser (cordial). Results analysed ordinary linear regression models generalized estimating equation modelling. Serum higher clinically isolated syndrome or remitting secondary primary progressive than controls (age adjusted P < 0.001 for both). above 90th percentile values independent predictor Expanded Disability Status Scale subsequent year (P 0.001). The probability gradually increased category. Contrast enhancing new/enlarging lesions independently associated (17.8% 4.9% increase per lesion respectively; level, more pronounced loss: 97.5th additional average loss 1.5% 0.001) 2.5% over 5 years = 0.009). correlated concurrent severity. High both are real-time, easy measure that conceptually comprehensive MRI.

Language: Английский

Citations

425
Blood-based NfL DOI Creative Commons
Oskar Hansson,

Shorena Janelidze,

Sara Hall

et al.

Neurology, Journal Year: 2017, Volume and Issue: 88(10), P. 930 - 937

Published: Feb. 9, 2017

Objective:

To determine if blood neurofilament light chain (NfL) protein can discriminate between Parkinson disease (PD) and atypical parkinsonian disorders (APD) with equally high diagnostic accuracy as CSF NfL, therefore improve the workup of disorders.

Methods:

The study included 3 independent prospective cohorts: Lund (n = 278) London 117) cohorts, comprising healthy controls patients PD, progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), multiple system atrophy (MSA), well an early cohort 109) PSP, MSA, or CBS duration ≤3 years. Blood NfL concentration was measured using ultrasensitive single molecule array (Simoa) method, to distinguish PD from APD investigated.

Results:

We found strong correlations concentrations (ρ ≥ 0.73–0.84, p ≤ 0.001). increased in (i.e., all groups) when compared cohorts (p < Furthermore, cohort, could accurately (area under curve [AUC] 0.91) similar results both (AUC 0.85) 0.81).

Conclusions:

Quantification be used APD. Blood-based might consequently symptoms primary care specialized clinics.

Classification evidence:

This provides Class III evidence that levels

Language: Английский

Citations

422
Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches DOI
Adam L. Boxer, Jin‐Tai Yu, Lawrence I. Golbe

et al.

The Lancet Neurology, Journal Year: 2017, Volume and Issue: 16(7), P. 552 - 563

Published: June 14, 2017

Language: Английский

Citations

402
Blood plasma phosphorylated-tau isoforms track CNS change in Alzheimer’s disease DOI Creative Commons
Nicolas R. Barthélemy, Kanta Horie, Chihiro Sato

et al.

The Journal of Experimental Medicine, Journal Year: 2020, Volume and Issue: 217(11)

Published: July 28, 2020

Highly sensitive and specific plasma biomarkers for Alzheimer’s disease (AD) have the potential to improve diagnostic accuracy in clinic facilitate research studies including enrollment prevention treatment trials. We recently reported CSF tau hyperphosphorylation, especially on T217, is an accurate predictor of β-amyloidosis at asymptomatic symptomatic stages. In current study, we determine by mass spectrometry utility p-tau isoforms detect AD pathology investigate isoforms’ profile relationships. Plasma was truncated as previously described CSF. measures p-tau-217 p-tau-181 were correlated. No correlation found between total-tau levels pS202 measures. highly amyloid plaque discovery cohort (n = 36, AUROC 0.99 0.98 respectively). validation 92), still status (AUROC 0.92), less 0.75).

Language: Английский

Citations

336
Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia DOI Creative Commons
Neil Graham, David Sharp

Journal of Neurology Neurosurgery & Psychiatry, Journal Year: 2019, Volume and Issue: 90(11), P. 1221 - 1233

Published: Sept. 21, 2019

Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer’s disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal is implicated in disrupting microtubule function, providing the potential context for pathologies tau and amyloid develop. neuropathology post-traumatic dementias well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis dementia problematic. It often difficult disentangle direct effects TBI from those produced progressive or other sequelae such as psychiatric impairment. CTE only be confidently identified at postmortem patients confused anxious about most likely cause their problems. A new approach assessment long-term needed. Accurate methods available investigation neurodegenerative conditions. These should systematically employed TBI. MRI positron emission tomography neuroimaging provide biomarkers may particular use postinjury setting. Brain atrophy a key measure disease progression used accurately quantify neuronal loss. Fluid neurofilament light complement neuroimaging, representing sensitive track processes that develop after could characterise endophenotypes associated distinct types neurodegeneration. In addition, they might profitably trials neuroprotective disease-modifying treatments, improving trial design precise measures

Language: Английский

Citations

282