scholarly journals Peran Neurofilament Light Chain sebagai Biomarker Prediktor Risiko Cognitive Impairment pada Penderita Chronic Kidney Disease

2019 ◽  
Vol 2 (3) ◽  
pp. 7-8
Author(s):  
Nella Rosyalina Damayanti ◽  
Divayari Gardiani
Keyword(s):  
Chronic Kidney Disease ◽  
Cognitive Impairment ◽  
Kidney Disease ◽  
Single Molecule ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

Latar Belakang: Chronic Kidney Disease (CKD) dapat menyebabkan cognitive impairment yang dapat menurunkan kualitas hidup dan kesejahteraan emosional pasien. Neurofilament Light Chain (NF-L) merupakan protein yang terletak di aksoplasma yang berperan menjaga struktur neuron. Diskusi: Defisit kognitif yang terjadi pada pasien dengan CKD diakibatkan toksin uremik yang menyebabkan cedera saraf. Prevalensi defisit kognitif berkisar 20-50% pada pasien CKD moderat dan 70% pada pasien CKD berat/ menjalani dialisis. Penurunan fungsi kognitif memiliki korelasi positif dengan penurunan eGFR pada pasien CKD. Kadar NF-L serum ditemukan mengalami peningkatan pada pasien setelah cedera akut pada otak seperti iskemia, perdarahan, dan pada pasien dengan penyakit neurodegeneratif seperti Alzheimer, dibandingkan pada individu sehat. Kadar NF-L serum dapat dideteksi dengan menggunakan pengujian single molecule array (Simoa). Simpulan: Pemeriksaan NF-L dapat dijadikan biomarker terjadinya defisit kognitif pada pasien CKD. Kata Kunci: Chronic Kidney Disease, Neurofilament Light Chain, Fungsi Kognitif, Biomarker

scholarly journals Elevated Levels of Serum Neurofilament Light Chain Associated with Cognitive Impairment in Vascular Dementia

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Weibin Ma ◽  
Jingjing Zhang ◽  
Jialei Xu ◽  
Depeng Feng ◽  
Xiaoling Wang ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Single Molecule ◽  
Light Chain ◽  
Peripheral Blood ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Biochemical Characteristics ◽  
Significant Difference

Objective. Vascular dementia (VaD) is a progressive neurodegenerative disease with cognitive decline caused by cerebrovascular factors. Despite the great progress made in the past decade, VaD still lacks effective treatments and peripheral blood biomarkers. In this study, we tested the level of peripheral blood neurofilament light chain (NfL) in VaD patients and explored its relationship with cognitive impairment. Method. A total of 176 study subjects including 80 normal controls (NC) and 96 VaD patients were included in our study. Upon admission, we collected clinical and biochemical characteristics of all research subjects. We also evaluate the Montreal cognitive assessment scale (MoCA) scores of all subjects. The serum NfL level was measured by the single-molecule array (Simoa) method. Results. The years of education in the NC group and VaD group were ( 11.65 ± 3.04 ) years and ( 10.53 ± 3.87 ) years, respectively. Compared with VaD patients, the NC group has a higher level of education ( p = 0.037 ). Furthermore, the results of Simoa indicated that VaD subjects had higher serum NfL levels compared with the NC group [( 8.49 ± 2.37 ) pg/ml vs. ( 19.26 ± 4.71 ) pg/ml, p < 0.001 ]. In terms of other clinical and biochemical characteristics, there was no significant difference between VaD and NC. The Spearman correlation analysis indicated that educational years have a significant positive correlation with MoCA scores ( r = 0.238 , p = 0.041 ), while age and serum NfL levels have a significantly negative correlation with MoCA scores (age: r = − 0.213 , p = 0.040 ; NfL: r = − 0.395 , p = 0.027 ). However, further multiple regression analysis showed that only serum NfL level might serve as an independent risk factor for cognitive decline in VaD ( β = 0.317 , p = 0.021 ). Conclusion. The serum NfL levels in VaD subjects are significantly elevated, which may be used as a potential peripheral blood marker for predicting cognitive impairment in patients with VaD.

Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease

2021 ◽  
Author(s):  
Ellen van der Plas ◽  
Olivia Lullmann ◽  
Lauren Hopkins ◽  
Jordan L. Schultz ◽  
Peggy C. Nopoulos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Light Chain ◽  
Brain Structure ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Plasma NfL levels and longitudinal change rates in C9orf72 and GRN-associated diseases: from tailored references to clinical applications

2021 ◽  
pp. jnnp-2021-326914
Author(s):  
Dario Saracino ◽  
Karim Dorgham ◽  
Agnès Camuzat ◽  
Daisy Rinaldi ◽  
Armelle Rametti-Lacroux ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Rate Of Change ◽  
Longitudinal Change ◽  
Youden Index ◽  
Clinical Genetic ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Link Type ◽  
Therapeutic Trials

ObjectiveNeurofilament light chain (NfL) is a promising biomarker in genetic frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). We evaluated plasma neurofilament light chain (pNfL) levels in controls, and their longitudinal trajectories in C9orf72 and GRN cohorts from presymptomatic to clinical stages.MethodsWe analysed pNfL using Single Molecule Array (SiMoA) in 668 samples (352 baseline and 316 follow-up) of C9orf72 and GRN patients, presymptomatic carriers (PS) and controls aged between 21 and 83. They were longitudinally evaluated over a period of >2 years, during which four PS became prodromal/symptomatic. Associations between pNfL and clinical–genetic variables, and longitudinal NfL changes, were investigated using generalised and linear mixed-effects models. Optimal cut-offs were determined using the Youden Index.ResultspNfL levels increased with age in controls, from ~5 to~18 pg/mL (p<0.0001), progressing over time (mean annualised rate of change (ARC): +3.9%/year, p<0.0001). Patients displayed higher levels and greater longitudinal progression (ARC: +26.7%, p<0.0001), with gene-specific trajectories. GRN patients had higher levels than C9orf72 (86.21 vs 39.49 pg/mL, p=0.014), and greater progression rates (ARC:+29.3% vs +24.7%; p=0.016). In C9orf72 patients, levels were associated with the phenotype (ALS: 71.76 pg/mL, FTD: 37.16, psychiatric: 15.3; p=0.003) and remarkably lower in slowly progressive patients (24.11, ARC: +2.5%; p=0.05). Mean ARC was +3.2% in PS and +7.3% in prodromal carriers. We proposed gene-specific cut-offs differentiating patients from controls by decades.ConclusionsThis study highlights the importance of gene-specific and age-specific references for clinical and therapeutic trials in genetic FTD/ALS. It supports the usefulness of repeating pNfL measurements and considering ARC as a prognostic marker of disease progression.Trial registration numbersNCT02590276 and NCT04014673.

Sustained reduction of serum neurofilament light chain over 7 years by alemtuzumab in early relapsing–remitting MS

2021 ◽  
pp. 135245852110323
Author(s):  
Jens Kuhle ◽  
Nadia Daizadeh ◽  
Pascal Benkert ◽  
Aleksandra Maceski ◽  
Christian Barro ◽  
...  
Keyword(s):  
Single Molecule ◽  
Light Chain ◽  
Interferon Beta ◽  
Efficacy And Safety ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Highly Active ◽  
Sustained Reduction ◽  
Relapsing Remitting ◽  
Healthy Control

Background: Alemtuzumab efficacy and safety was demonstrated in CARE-MS I and extension studies (CAMMS03409; TOPAZ). Objective: Evaluate serum neurofilament light chain (sNfL) in CARE-MS I patients and highly active disease (HAD) subgroup, over 7 and 2 years for alemtuzumab and subcutaneous interferon beta-1a (SC IFNB-1a), respectively. Methods: Patients received SC IFNB-1a 44 µg 3×/week or alemtuzumab 12 mg/day at baseline and month 12, with further as-needed 3-day courses. sNfL was measured using single-molecule array (Simoa™). HAD definition was ⩾2 relapses in year before randomization and ⩾1 baseline gadolinium-enhancing lesion. Results: Baseline median sNfL levels were similar in alemtuzumab ( n = 354) and SC IFNB-1a–treated ( n = 159) patients (31.7 vs 31.4 pg/mL), but decreased with alemtuzumab versus SC IFNB-1a until year 2 (Y2; 13.2 vs 18.7 pg/mL; p < 0.0001); 12.7 pg/mL for alemtuzumab at Y7. Alemtuzumab-treated patients had sNfL at/below healthy control median at Y2 (72% vs 47%; p < 0.0001); 73% for alemtuzumab at Y7. HAD patients ( n = 102) had higher baseline sNfL (49.4 pg/mL) versus overall population; alemtuzumab HAD patients attained similar levels (Y2, 12.8 pg/mL; Y7, 12.7 pg/mL; 75% were at/below control median at Y7). Conclusion: Alemtuzumab was superior to SC IFNB-1a in reducing sNfL, with levels in alemtuzumab patients remaining stable through Y7. ClinicalTrials.gov identifier: NCT00530348, NCT00930553, NCT02255656

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 Cerebrospinal fluid neurofilament light chain tracks cognitive impairment in multiple sclerosis

2019 ◽  
Vol 266 (9) ◽  
pp. 2157-2163 ◽  
Author(s):  
Lorenzo Gaetani ◽  
Nicola Salvadori ◽  
Viviana Lisetti ◽  
Paolo Eusebi ◽  
Andrea Mancini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Cognitive Impairment ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Thirty years after anorexia nervosa onset, serum neurofilament light chain protein concentration indicates neuronal injury

2020 ◽  
Author(s):  
Elisabet Wentz ◽  
Sandra Rydberg Dobrescu ◽  
Lisa Dinkler ◽  
Carina Gillberg ◽  
Christopher Gillberg ◽  
...  
Keyword(s):  
Anorexia Nervosa ◽  
Single Molecule ◽  
Light Chain ◽  
Axonal Degeneration ◽  
Neuronal Injury ◽  
Serum Levels ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
National Patient ◽  
History Of

Abstract Little is known about the long-term consequences of anorexia nervosa (AN) in terms of possible brain neuronal injury. We aimed at investigating whether women with adolescent-onset AN exhibit increased serum levels of neurofilament light chain protein (NfL), a biomarker for neuronal injury, compared with matched controls at 30-year follow-up. Blood samples were collected from 34 women with adolescent-onset AN and 38 matched healthy comparison women (COMP), at a mean age of 44 years (range 38–48 years). NfL was measured in serum using the in-house single molecule array (Simoa) method. The individuals were asked whether they or their parents had been diagnosed with dementia. The Swedish National Patient Register was searched for diagnoses related to dementia. Serum NfL concentrations were significantly higher in the AN group (AN 27.7 pg/ml; COMP 19.0 pg/ml; p = 0.041). When individuals with medical/neurological disorders in the AN and COMP groups were excluded, there was a statistically non-significant trend towards higher concentrations in the AN group (AN 27.4 pg/ml; COMP 18.8 pg/ml; p = 0.060). None of the participants had been diagnosed with dementia. There was no significant correlation between serum NfL and AN duration (r = 0.15). There was a moderate negative correlation between the serum NfL concentration and the current BMI in the AN group (r = 0.44). This is the first time that serum NfL has been assessed in middle-aged women with a history of adolescent-onset AN. The results suggest that there might be increased axonal degeneration as a sequel of AN. Individuals remaining underweight had higher serum NfL concentrations than those with a normal/high BMI. Additional studies are needed to confirm increased serum NfL concentrations in individuals recovered from AN. There is a need for further study of axonal degeneration as a consequence of AN.

Sign in / Sign up

Export Citation Format

Share Document