scholarly journals Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from phenocopy non-progressors

2022 ◽  
Author(s):  
Dhamidhu Eratne ◽  
Michael Keem ◽  
Courtney Lewis ◽  
Matthew Kang ◽  
Mark Walterfang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Frontotemporal Dementia ◽  
Light Chain ◽  
Area Under The Curve ◽  
Final Diagnosis ◽  
Healthcare Services ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Clinical Dilemma ◽  
T Tau

Background: Distinguishing behavioural variant frontotemporal dementia (bvFTD) from non-neurodegenerative non-progressor, phenocopy mimics of frontal lobe dysfunction, can be one of the most challenging clinical dilemmas. A biomarker of neuronal injury, neurofilament light chain (NfL), could reduce misdiagnosis and delay. Methods: Cerebrospinal fluid (CSF) NfL, amyloid beta 1-42 (AB42), total and phosphorylated tau (T-tau, P-tau) levels were examined in patients with an initial diagnosis of bvFTD. Based on follow up information, patients were categorised as Progressors. Non-Progressors were subtyped in to Phenocopy Non-Progressors (non-neurological/neurodegenerative final diagnosis), and Static Non-Progressors (static deficits, not fully explained by non-neurological/neurodegenerative causes). Results: Forty-three patients were included: 20 Progressors, 23 Non-Progressors (15 Phenocopy, 8 Static), 20 controls. NfL concentrations were lower in Non-Progressors (Non-Progressors Mean, M=554pg/mL, 95%CI:[461, 675], Phenocopy Non-Progressors M=459pg/mL, 95%CI:[385, 539], Static Non-Progressors M=730pg/mL, 95%CI:[516, 940]), compared to bvFTD Progressors (M=2397pg/mL, 95%CI:[1607, 3332]). NfL distinguished Progressors from Non-Progressors with the highest accuracy (area under the curve 0.92, 90%/87% sensitivity/specificity, 86%/91% positive/negative predictive value, 88% accuracy). Static Non-Progressors tended to have higher T-tau and P-tau levels compared to Phenocopy Non-Progressors. Conclusion: This study demonstrated strong diagnostic utility of CSF NfL to distinguish bvFTD from phenocopy non-progressor variants, at baseline, with high accuracy, in a real-world clinical setting. This has important clinical implications, to improve outcomes for patients and clinicians facing this challenging clinical dilemma, as well as for healthcare services, and clinical trials. Further research is required to investigate heterogeneity within the non-progressor group and potential diagnostic algorithms, and prospective studies are underway assessing plasma NfL

scholarly journals Cerebrospinal fluid neurofilament light chain protein levels in subtypes of frontotemporal dementia

BMC Neurology ◽  
2013 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Landqvist Waldö ◽  
Alexander Frizell Santillo ◽  
Ulla Passant ◽  
Henrik Zetterberg ◽  
Lars Rosengren ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Frontotemporal Dementia ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Protein Levels

scholarly journals Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies

2019 ◽  
Vol 90 (9) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah-Jane Martin ◽  
Sarah McGlasson ◽  
David Hunt ◽  
James Overell
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Meta Analysis ◽  
Grey Literature ◽  
Case Control ◽  
Disease Stage ◽  
Case Control Studies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

ObjectiveNeurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.MethodsGuidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.ResultsCSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).ConclusionsCSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.

scholarly journals ATN incorporating cerebrospinal fluid neurofilament light chain detects frontotemporal lobar degeneration

2020 ◽  
Author(s):  
Katheryn A.Q. Cousins ◽  
Jeffrey S. Phillips ◽  
David J. Irwin ◽  
Edward B. Lee ◽  
David A. Wolk ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Frontotemporal Lobar Degeneration ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Elevated Neurofilament Light Chain in Cerebrospinal Fluid and Plasma Reflect Inflammatory MRI Activity in Neurosarcoidosis

2021 ◽  
Vol 11 (2) ◽  
pp. 238
Author(s):  
Keld-Erik Byg ◽  
Helle H. Nielsen ◽  
Tobias Sejbaek ◽  
Jonna Skov Madsen ◽  
Dorte Aalund Olsen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Light Chain ◽  
Plasma Levels ◽  
Healthy Controls ◽  
Neurofilament Light Chain ◽  
Neurofilament Light ◽  
Potential Biomarker ◽  
Fluid Levels

Background: Damage to axonal cells releases neurofilament light chain (NFL) into the cerebrospinal fluid and plasma. The objective of this study was to investigate NFL as a potential biomarker of disease activity in neurosarcoidosis. MRIs were graded according to enhancing lesions at different central nervous system (CNS) sites. Results: In cerebrospinal fluid, levels of NFL were higher in neurosarcoidosis patients (n = 20) median 2304 pg/mL (interquartile range (IQR) 630–19,612) compared to 426 pg/mL (IQR 261-571) in extra-neurologic sarcoidosis patients (n = 20) and 336 pg/mL (IQR 194–402) in healthy controls (n = 11) (p = 0.0002). In plasma, levels of NFL were higher in neurosarcoidosis patients median 28.2 pg/mL (IQR 11.5–49.3) compared to 6.2 pg/mL (IQR 4.3–8.2) in extra-neurologic sarcoidosis patients and 7.1 pg/mL (IQR 6.2–9.0) in healthy controls (p = 0.0001). Levels in both cerebrospinal fluid and plasma were higher in neurosarcoidosis patients with moderate/severe enhancement than patients with mild enhancement on MRI (p = 0.009 and p = 0.005, respectively). To distinguish neurosarcoidosis patients from extra-neurologic patients and healthy controls, a cut-off level of 630 pg/mL in cerebrospinal fluid had 94% specificity and 79% sensitivity, while a cut-off level of 11.4 pg/mL in plasma had 97% specificity and 75% sensitivity. Conclusions: NFL levels in cerebrospinal fluid and plasma are significantly higher in neurosarcoidosis patients compared to extra-neurologic patients and healthy controls, and the levels correlate to the extent of inflammation on MRI.

scholarly journals Evaluation of Cerebrospinal Fluid Neurofilament Light Chain as a Routine Biomarker in a Memory Clinic

2018 ◽  
Vol 74 (4) ◽  
pp. 442-445 ◽  
Author(s):  
Matías Niikado ◽  
Patricio Chrem-Méndez ◽  
Tatiana Itzcovich ◽  
Micaela Barbieri-Kennedy ◽  
Ismael Calandri ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Memory Clinic ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Neurofilament light chain: a biomarker for genetic frontotemporal dementia

2016 ◽  
Vol 3 (8) ◽  
pp. 623-636 ◽  
Author(s):  
Lieke H. Meeter ◽  
Elise G. Dopper ◽  
Lize C. Jiskoot ◽  
Raquel Sanchez-Valle ◽  
Caroline Graff ◽  
...  
Keyword(s):  
Frontotemporal Dementia ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Tracking neurodegeneration in frontotemporal dementia and Alzheimer’s disease: A comparative study of plasma tau and neurofilament light chain

2020 ◽  
Vol 16 (S5) ◽  
Author(s):  
Ignacio Illán‐Gala ◽  
Alberto Lleó ◽  
Anna M. Karydas ◽  
Adam M. Staffaroni ◽  
Henrik Zetterberg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Comparative Study ◽  
Frontotemporal Dementia ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals P4-218: SEX DIFFERENCES IN CEREBROSPINAL FLUID NEUROFILAMENT LIGHT CHAIN LEVELS ARE CONSISTENT ACROSS COHORTS

2019 ◽  
Vol 15 ◽  
pp. P1359-P1360
Author(s):  
Daniel Alcolea ◽  
Eduard Vilaplana ◽  
Laia Muñoz-Llahuna ◽  
Ignacio Illán-Gala ◽  
Estrella Morenas-Rodríguez ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Sex Differences ◽  
Light Chain ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

scholarly journals Neurofilament light chain in the vitreous humor of the eye

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Manju L. Subramanian ◽  
Viha Vig ◽  
Jaeyoon Chung ◽  
Marissa G. Fiorello ◽  
Weiming Xia ◽  
...  
Keyword(s):  
Sex Education ◽  
Inflammatory Cytokines ◽  
Amyloid Beta ◽  
Light Chain ◽  
Systemic Disease ◽  
Vitreous Humor ◽  
Neurofilament Light Chain ◽  
Cross Sectional ◽  
Neurofilament Light ◽  
T Tau

Abstract Background Neurofilament light chain (NfL) is a promising biomarker of neurodegeneration in the cerebrospinal fluid and blood. This study investigated the presence of NfL in the vitreous humor and its associations with amyloid beta, tau, inflammatory cytokines and vascular proteins, apolipoprotein E (APOE) genotypes, Mini-Mental State Examination (MMSE) scores, systemic disease, and ophthalmic diseases. Methods This is a single-site, prospective, cross-sectional cohort study. Undiluted vitreous fluid (0.5–1.0 mL) was aspirated during vitrectomy, and whole blood was drawn for APOE genotyping. NfL, amyloid beta (Aβ), total Tau (t-Tau), phosphorylated Tau (p-Tau181), inflammatory cytokines, chemokines, and vascular proteins in the vitreous were quantitatively measured by immunoassay. The main outcome measures were the detection of NfL levels in the vitreous humor and its associations with the aforementioned proteins. Linear regression was used to test the associations of NfL with other proteins, APOE genotypes, MMSE scores, and ophthalmic and systemic diseases after adjustment for age, sex, education level, and other eye diseases. Results NfL was detected in all 77 vitreous samples. NfL was not found to be associated with ophthalmic conditions, APOE genotypes, MMSE scores, or systemic disease (p > 0.05). NfL levels were positively associated with increased vitreous levels of Aβ40 (p = 7.7 × 10−5), Aβ42 (p = 2.8 × 10−4), and t-tau (p = 5.5 × 10−7), but not with p-tau181 (p = 0.53). NfL also had significant associations with inflammatory cytokines such as interleukin-15 (IL-15, p = 5.3 × 10−4), IL-16 (p = 2.2 × 10−4), monocyte chemoattractant protein-1 (MCP1, p = 4.1 × 10−4), and vascular proteins such as vascular endothelial growth factor receptor-1 (VEGFR1, p = 2.9 × 10−6), Vegf-C (p = 8.6 × 10−6), vascular cell adhesion molecule-1 (VCAM-1, p = 5.0 × 10−4), Tie-2 (p = 6.3 × 10−4), and intracellular adhesion molecular-1 (ICAM-1, p = 1.6 × 10−4). Conclusion NfL is detectable in the vitreous humor of the eye and significantly associated with amyloid beta, t-tau, and select inflammatory and vascular proteins in the vitreous. Additionally, NfL was not associated with patients’ clinical eye condition. Our results serve as a foundation for further investigation of NfL in the ocular fluids to inform us about the potential utility of its presence in the eye.

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