Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases

Zerr, Inga; Schmitz, Matthias; Karch, André; Villar‐Piqué, Anna; Kanata, Ειrini; Golanska, Ewa; Díaz-Lucena, Daniela; Karsanidou, Aikaterini; Hermann, Péter; Knipper, Tobias; Goebel, Stefan; Varges, Daniela; Sklaviadis, Theodoros; Sikorska, Beata; Liberski, Paweł P.; Santana, Isabel; Ferrer, Isidro; Zetterberg, Henrik; Blennow, Kaj; Calero, Olga; Calero, Miguel; Ladogana, Anna; Sánchez‐Valle, Raquel; Baldeiras, Inês; Llorens, Franc

doi:10.1016/j.jalz.2017.12.008

Cited by 75 publications

(93 citation statements)

References 72 publications

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“…Differently from what has been reported for CSF, we could not find a significant difference in serum NFL values between AD and FTD 26. This might be caused by the lower number of patients with AD and FTD in our cohort; moreover, our patients with FTD might be at an earlier disease stage with less brain atrophy.…”

Section: Discussioncontrasting

confidence: 99%

Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Verde¹,

Steinacker

Weishaupt

et al. 2018

J Neurol Neurosurg Psychiatry

204

179

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ObjectiveTo determine the diagnostic and prognostic performance of serum neurofilament light chain (NFL) in amyotrophic lateral sclerosis (ALS).MethodsThis single-centre, prospective, longitudinal study included the following patients: 124 patients with ALS; 50 patients without neurodegenerative diseases; 44 patients with conditions included in the differential diagnosis of ALS (disease controls); 65 patients with other neurodegenerative diseases (20 with frontotemporal dementia, 20 with Alzheimer’s disease, 19 with Parkinson’s disease, 6 with Creutzfeldt-Jakob disease (CJD)). Serum NFL levels were measured using the ultrasensitive single molecule array (Simoa) technology.ResultsSerum NFL levels were higher in ALS in comparison to all other categories except for CJD. A cut-off level of 62 pg/mL discriminated between ALS and all other conditions with 85.5% sensitivity (95% CI 78% to 91.2%) and 81.8% specificity (95% CI 74.9% to 87.4%). Among patients with ALS, serum NFL correlated positively with disease progression rate (rs=0.336, 95% CI 0.14 to 0.506, p=0.0008), and higher levels were associated with shorter survival (p=0.0054). Serum NFL did not differ among patients in different ALS pathological stages as evaluated by diffusion-tensor imaging, and in single patients NFL levels were stable over time.ConclusionsSerum NFL is increased in ALS in comparison to other conditions and can serve as diagnostic and prognostic biomarker. We established a cut-off level for the diagnosis of ALS.

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Section: Discussioncontrasting

confidence: 99%

Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Verde¹,

Steinacker

Weishaupt

et al. 2018

J Neurol Neurosurg Psychiatry

204

179

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“…In concordance to previously published data, we have found an increase in NF‐L in all types of neurodegenerative dementia evaluated, suggesting that CSF NF‐L is a non‐disease‐specific biomarker . In agreement with previous studies, CSF NF‐L was higher in FTD than in AD .…”

Section: Discussionsupporting

confidence: 92%

“…Other CSF biomarkers are being studied in AD and other neurodegenerative dementias. Neurofilament light (NF‐L) is a major cytoskeletal constituent of neuronal cells and can be released into the CSF, detecting significant increases in different neurologic disorders . Neurogranin (Ng) is a calmodulin‐binding postsynaptic neuronal protein that is abundantly expressed in perikaryal and dendritic cytoplasm, involved in modulating synaptic transmission and plasticity mechanisms .…”

Section: Introductionmentioning

confidence: 99%

“…Neurofilament light (NF-L) is a major cytoskeletal constituent of neuronal cells and can be released into the CSF, detecting significant increases in different neurologic disorders. [9][10][11][12][13][14][15][16][17] Neurogranin (Ng) is a calmodulin-binding postsynaptic neuronal protein that is abundantly expressed in perikaryal and dendritic cytoplasm, 18 involved in modulating synaptic transmission and plasticity mechanisms. [19][20][21][22][23] The 14-3-3 proteins are highly expressed in the brain and some of the 14-3-3 isoforms are particularly enriched in the presynapses, to regulate transmission and plasticity.…”

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confidence: 99%

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Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

Antonell

Tort‐Merino

Ríos

et al. 2020

Alzheimer's & Dementia

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Introduction: Synaptic damage, axonal neurodegeneration, and neuroinflammation are common features in Alzheimer's disease (AD), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD). Methods: Unicentric cohort of 353 participants included healthy control (HC) subjects, AD continuum stages, genetic AD and FTD, and FTD and CJD. We measured cerebrospinal fluid neurofilament light (NF-L), neurogranin (Ng), 14-3-3, and YKL-40 proteins.Results: Biomarkers showed differences in HC subjects versus AD, FTD, and CJD. Disease groups differed between them except AD versus FTD for YKL-40. Only NF-L differed between all stages within the AD continuum. AD and FTD symptomatic mutation carriers presented differences with respect to HC subjects. Applying the AT(N) system, 96% subjects were positive for neurodegeneration if 14-3-3 was used, 94% if NF-L was used, 62% if Ng was used, and 53% if YKL-40 was used.

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“…In the remaining 11 studies, with 2404 AD cases and 1647 disease mimic controls, CSF NfL concentration was not statistically distinguishable between AD cases and disease mimic controls (average ratio 0.87, 95% CI 0.70–1.08, P = 0.175; Fig. 2C) [16,23,27,28,33,35,40,43,45,46].…”

Section: Resultsmentioning

confidence: 96%

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

Forgrave

Huei‐Ming

Best

et al. 2019

Alz & Dem Diag Ass & Dis Mo

121

134

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Introduction A systematic review and meta‐analysis was performed regarding the diagnostic performance of neurofilament light chain (NfL) in CSF and blood. Methods A database search was conducted for NfL biomarker studies in the context of Alzheimer's disease (AD), frontotemporal dementia (FTD), and amyotrophic lateral sclerosis (ALS) compared with controls (i.e., cognitively unimpaired, mild cognitive impairment, or disease mimics). Results In groups with a sufficient number of studies, the performance of NfL in blood and CSF was similar. Compared with disease mimics, we observed that CSF NfL had strong discriminatory power for ALS, modest discriminatory power for FTD, and no discriminatory power for AD. NfL provided the greatest separation between ALS and cognitively unimpaired controls in both the blood and CSF, followed by FTD (CSF and blood), then AD (blood and CSF). Discussion Comparable performance of CSF and blood NfL in many groups demonstrates the promise of NfL as a noninvasive biomarker of neurodegeneration; however, its utility in clinically meaningful scenarios requires greater scrutiny. Toward clinical implementation, a more comprehensive understanding of NfL concentrations in disease subtypes with overlapping phenotypes and at defined stages of disease, and the development of a harmonization program, are warranted.

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Cerebrospinal fluid neurofilament light levels in neurodegenerative dementia: Evaluation of diagnostic accuracy in the differential diagnosis of prion diseases

Abstract: Increased NFL levels are a common feature in neurodegenerative dementias.

Cited by 75 publications

References 72 publications

Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis

Synaptic, axonal damage and inflammatory cerebrospinal fluid biomarkers in neurodegenerative dementias

The diagnostic performance of neurofilament light chain in CSF and blood for Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis: A systematic review and meta‐analysis

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