scholarly journals Plasma Neurofilament Light Chain Predicts Cognitive Progression in Prodromal and Clinical Dementia with Lewy Bodies

2021 ◽  
pp. 1-7
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex, and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

scholarly journals Plasma Neurofilament Light Chain predicts cognitive progression in prodromal and clinical dementia with Lewy Bodies

2021 ◽  
Author(s):  
Andrea Pilotto ◽  
Alberto Imarisio ◽  
Claudia Carrarini ◽  
Mirella Russo ◽  
Stefano Masciocchi ◽  
...  
Keyword(s):  
Light Chain ◽  
Neurological Disorders ◽  
Dementia With Lewy Bodies ◽  
Neuronal Damage ◽  
Lewy Bodies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Predict Disease Progression

Plasma neurofilament light chain (NfL) is a marker of neuronal damage in different neurological disorders and might predict disease progression in dementia with Lewy bodies (DLB). The study enrolled 45 controls and 44 DLB patients (including 17 prodromal cases) who underwent an extensive assessment at baseline and at 2 years follow-up. At baseline, plasma NfL levels were higher in both probable DLB and prodromal cases compared to controls. Plasma NfL emerged as the best predictor of cognitive decline compared to age, sex and baseline severity variables. The study supports the role of plasma NfL as a useful prognostic biomarker from the early stages of DLB.

Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012632
Author(s):  
Kjetil Bjornevik ◽  
Eilis J. O'Reilly ◽  
Samantha Molsberry ◽  
Laurence N. Kolonel ◽  
Loic Le Marchand ◽  
...  
Keyword(s):  
Light Chain ◽  
Conditional Logistic Regression ◽  
Disease Diagnosis ◽  
Health Study ◽  
Plasma Samples ◽  
Blood Draw ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Rate Ratios

Objective:To assess whether plasma neurofilament light chain (NfL) levels are elevated before ALS diagnosis and to evaluate whether pre-diagnostic NfL levels are associated with metabolic alterations.Methods:We conducted a matched case-control study nested in three large prospective US cohorts (the Nurses’ Health Study, the Health Professionals Follow-up Study, and the Multiethnic Cohort Study), and identified 84 individuals who developed ALS during follow-up and had available plasma samples prior to disease diagnosis. For each ALS case, we randomly selected controls from those who were alive at the time of the case diagnosis and matched on birth year, sex, race/ethnicity, fasting status, cohort, and time of blood draw. We measured NfL in the plasma samples and used conditional logistic regression to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for ALS, adjusting for body mass index, smoking, physical activity, and urate levels.Results:Higher NfL levels were associated with a higher ALS risk in plasma samples collected within 5 years of the ALS diagnosis (RR per 1 standard deviation [SD] increase: 2.68, 95% CI: 1.18-6.08), but not in samples collected further away from the diagnosis (RR per 1 SD increase 1.16, 95% CI: 0.78-1.73). A total of 21 metabolites were correlated with pre-diagnostic NfL levels in ALS cases (p < 0.05), but none of these remained significant after multiple comparison adjustments.Conclusions:Plasma NfL levels were elevated in pre-diagnostic ALS cases, indicating that NfL may be a useful biomarker already in the earliest stages of the disease.Classification of Evidence:This study provides Class II evidence that plasma NfL levels are elevated in pre-diagnostic ALS patients.

scholarly journals No evidence of neuronal damage as measured by neurofilament light chain in a HIV cure study utilising a kick-and-kill approach

2021 ◽  
pp. 100056
Author(s):  
Jasmini ALAGARATNAM ◽  
Wolfgang STÖHR ◽  
Jamie TOOMBS ◽  
Amanda HESLEGRAVE ◽  
Henrik ZETTERBERG ◽  
...  
Keyword(s):  
Light Chain ◽  
Neuronal Damage ◽  
Hiv Cure ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ngoc Dung Le ◽  
Lukas Muri ◽  
Denis Grandgirard ◽  
Jens Kuhle ◽  
David Leppert ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Light Chain ◽  
Pneumococcal Meningitis ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Health Concern ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Inflammatory Phase

Abstract Background Pneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM). Methods Eleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively. Results In ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics. Conclusion Current results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.

scholarly journals Plasma neurofilament light chain protein is not increased in treatment-resistant schizophrenia and first-degree relatives

2021 ◽  
pp. 000486742110586
Author(s):  
Dhamidhu Eratne ◽  
Shorena Janelidze ◽  
Charles B Malpas ◽  
Samantha Loi ◽  
Mark Walterfang ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Light Chain ◽  
Neurodegenerative Disorders ◽  
Neuronal Damage ◽  
First Episode ◽  
Treatment Resistant ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
First Degree Relatives ◽  
Frontotemporal Dementias

Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine ( n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine ( n = 13), and age- and sex-matched controls ( n = 59). Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman’s r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia ( r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight ( r = −0.305, 95% confidence interval: [−0.504, −0.076]). Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode.

scholarly journals CSF neurofilament light chain testing as an aid to determine treatment strategies in MS

2020 ◽  
Vol 7 (6) ◽  
pp. e880 ◽  
Author(s):  
Saúl Reyes ◽  
Ide Smets ◽  
David Holden ◽  
Karina Carrillo-Loza ◽  
Tatiana Christmas ◽  
...  
Keyword(s):  
Disease Activity ◽  
Light Chain ◽  
Clinical Care ◽  
Treatment Strategies ◽  
Oral Disease ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Treatment Escalation

ObjectiveTo evaluate the use of CSF neurofilament light chain (NfL) measurements in clinical practice as well as their effect on treatment strategies and outcomes in patients with MS.MethodsThis was an observational cohort study of patients with MS who had a CSF NfL measurement between December 2015 and July 2018 as part of their routine clinical care. Treatment strategies were classified as “No Treatment/No Escalation” (no treatment or no escalation of treatment) or “Treatment/Escalation” (first-line injectable/oral disease-modifying therapies (DMTs), highly active DMTs, or treatment escalation). Change in Expanded Disability Status Scale (EDSS) scores was evaluated after 1-year follow-up.ResultsOf 203 patients with MS, 117 (58%) had relapsing-remitting MS. Disease activity was most frequently indicated by elevated CSF NfL (n = 85), followed by clinical (n = 81) and MRI activity (n = 65). CSF NfL measurements were independently associated with clinical (p = 0.02) and MRI activity (p < 0.001). Of those with elevated CSF NfL as the only evidence of disease activity (n = 22), 77% had progressive MS (PMS). In patients with PMS, 17 (20%) had elevated CSF NfL as the sole indicator of disease activity. Elevated CSF NfL resulted more frequently in Treatment/Escalation than normal CSF NfL (p < 0.001). Median EDSS change at follow-up was similar between patients receiving No Treatment/No Escalation and Treatment/Escalation decisions (p = 0.81).ConclusionsCSF NfL measurements informed treatment strategies, alongside clinical and MRI measures. CSF NfL levels were the only indicator of disease activity in a subset of patients, which was more pronounced in patients with PMS. Elevated CSF NfL was associated with more Treatment/Escalation strategies, which had an impact on EDSS outcomes at 1 year.

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