Cerebrospinal fluid neurofilament light chain is elevated in Niemann–Pick type C compared to psychiatric disorders and healthy controls and may be a marker of treatment response

Eratne, Dhamidhu; Loi, Samantha M; Li, Qiao‐Xin; Varghese, Shiji; McGlade, Amelia; Collins, Steven J.; Masters, Colin L.; Velakoulis, Dennis; Walterfang, Mark

doi:10.1177/0004867419893431

Cited by 22 publications

(19 citation statements)

References 4 publications

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“…Furthermore, observed changes in NF-L levels of GD mice suggest that NF-L might not only be a valuable biomarker in classical neurodegenerative diseases but also in other diseases that have a neuronal component like some lysosomal storage diseases, e.g., GD, Pompe disease, Krabbe disease, or Sanfilippo syndrome. For patients of the lysosomal storage disease Niemann-Pick a first study that confirms the value of NF-L as CSF marker was just released (Eratne et al, 2019). Analysis of GD patients CSF and/or plasma will hence reveal, if NF-L could have a similar value for the measurement of disease progression as observed for ALS patients.…”

Section: Discussionmentioning

confidence: 92%

Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value

et al. 2020

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Neurofilament-light chain (NF-L) is a well-known clinical biomarker of many neurodegenerative diseases. By analyzing amyotrophic lateral sclerosis (ALS) patients cerebrospinal fluid (CSF) or plasma, progression of NF-L levels can forecast conversion from the presymptomatic to symptomatic stage and time of survival. The use of plasma for NF-L measurement makes this biomarker exceptionally valuable for clinical studies since sample collection can be performed repeatedly without causing much harm. Detailed analyses of NF-L expression in neurodegenerative disease patient's samples were already performed, while NF-L levels of preclinical models of ALS, Alzheimer's and Parkinson's disease as well as lysosomal storage diseases are still widely unknown. We therefore evaluated NF-L levels in the plasma of the ALS models SOD1-G93A low expressor and TAR6/6 mice, the Alzheimer's disease (AD) model 5xFAD, the Parkinson's disease model Line 61 and the Gaucher disease (GD) model 4L/PS-NA and the CSF of selected models. Our results show that NF-L levels are highly increased in the plasma of ALS, Alzheimer's and GD models, while in the analyzed Parkinson's disease model NF-L plasma levels barely changed. Most analyzed models show a progressive increase of NF-L levels. NF-L measurements in the plasma of the neurodegenerative disease mouse models of ALS and AD are thus a good tool to evaluate disease progression. Compared to analyses in human tissues, our results suggest a high translation value of murine NF-L levels and their progression. Furthermore, our data indicate that NF-L might also be a good biomarker for disorders with a neuronal component like some lysosomal storage diseases.

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Section: Discussionmentioning

confidence: 92%

Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value

et al. 2020

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“…Loeffler T, et al in a mouse model showed that NfL concentration can be a valuable biomarker not only in typical neurodegenerative diseases but also in other diseases that have an additional neuronal component, like lysosomal storage diseases, e.g., Gaucher disease (15). Erante D, et al confirmed that NfL is a good biomarker of neurodegeneration in Niemann-Pick disease (16). Ru Y, et al described NfL as a biomarker of neurodegeneration in neuronal ceroid lipofuscinosis type 2 (CLN2 disease), another lysosomal storage disease.…”

Section: Resultsmentioning

confidence: 98%

Serum neurofilament light chain is not a useful biomarker of central nervous system involvement in women with Fabry disease

Hołub

Kędzierska

Muras-Szwedziak

et al. 2021

IRDR

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“…Neurofilament light (NfL) is one of three subunits of a neuroaxonal cytoskeletal protein common to myelinated axons, with elevated levels in cerebrospinal fluid (CSF) and blood associated with neuronal injury and a marker of diagnosis, staging and prognosis, in a diverse range of neurological and neurodegenerative disorders [25][26][27][28][29][30][31]. Numerous studies have demonstrated elevated CSF and blood NfL in bvFTD compared to controls, as well as primary psychiatric disorders [29][30][31][32][33][34][35][36][37][38]. Recent expert consensus guidelines and recommendations have recommended NfL as a biomarker to assist with differentiating bvFTD from primary psychiatric disorders [11].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from ‘phenocopy’ non-progressors

Eratne

Keem²,

Lewis³

et al. 2022

Preprint

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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

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Cerebrospinal fluid neurofilament light chain is elevated in Niemann–Pick type C compared to psychiatric disorders and healthy controls and may be a marker of treatment response

Cited by 22 publications

References 4 publications

Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value

Neurofilament-Light Chain as Biomarker of Neurodegenerative and Rare Diseases With High Translational Value

Serum neurofilament light chain is not a useful biomarker of central nervous system involvement in women with Fabry disease

Cerebrospinal fluid neurofilament light chain differentiates behavioural variant frontotemporal dementia progressors from ‘phenocopy’ non-progressors

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