Serum neurofilament light chain in behavioral variant frontotemporal dementia

Steinacker, Petra; Anderl‐Straub, Sarah; Diehl‐Schmid, Janine; Semler, Elisa; Uttner, Ingo; Arnim, Christine A. F. Von; Barthel, Henryk; Danek, Adrian; Faßbender, Klaus; Fließbach, Klaus; Foerstl, Hans; Grimmer, Timo; Huppertz, Hans‐Jürgen; Jahn, Holger; Kassubek, Jan; Kornhuber, Johannes; Landwehrmeyer, G. Bernhard; Lauer, Martin; Maler, Juan Manuel; Mayer, Benjamin; Oeckl, Patrick; Prudlo, Johannes; Schneider, Anja; Volk, Alexander E; Wiltfang, Jens; Schroeter, Matthias L.; Ludolph, Albert C.; Otto, Markus

doi:10.1212/wnl.0000000000006318

Cited by 98 publications

(124 citation statements)

References 44 publications

(63 reference statements)

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“…3D) [9,51,59,63]. The remaining study investigated 74 FTD cases compared with 17 MCI controls [9], with an NfL concentration ratio of 2.95 (95% CI 2.22–3.92; Fig. 3E).…”

Section: Resultsmentioning

confidence: 99%

“…Twelve studies compared blood (i.e., plasma and serum) NfL concentration in AD cases and cognitively unimpaired controls [4,9,25,30,42,[47][48][49][50][51][52][53]; however, three of these studies used largely overlapping data from the ADNI database [49,50,53]. To avoid bias, the largest of the three overlapping studies was selected for inclusion in the meta-analysis [53]; thus, 10 studies comparing 471 AD cases to 518 cognitively unimpaired controls were included in the meta-analysis.…”

Section: Nfl In Admentioning

confidence: 99%

“…Of these studies, 5 studies (365 AD cases and 357 cognitively unimpaired controls) compared NfL concentration in plasma, with an average ratio of 2.11 (95% CI 0.78-5.73) [25,30,47,48,53]. The remaining 5 studies (106 AD cases and 161 cognitively unimpaired controls) compared serum NfL concentration [4,9,42,51,52], with an average ratio of 3.22 (95% CI 1.37-7.57). A between-subgroup comparison indicated that the NfL concentration ratio for AD to cognitively unimpaired controls was statistically indistinguishable in serum and plasma (Q (1) 5 0.80, P 5 0.371).…”

Section: Nfl In Admentioning

confidence: 99%

“…3A) [16][17][18][20][21][22][26][27][28]31,32,35,36,38,[44][45][46][54][55][56][57][58][59][60][61][62]. Four studies investigated 113 FTD cases and 110 MCI controls [9,22,43,44], with no observable difference in CSF NfL concentration (ROM 5 1.87, 95% CI 0.88-3.98, P 5 0.077; Fig. 3B).…”

Section: Nfl In Ftdmentioning

confidence: 99%

“…Five studies investigated blood NfL concentration in FTD cases compared with controls [4,9,51,59,63]. Four of these studies compared serum NfL concentration in 202 FTD cases and 139 cognitively unimpaired controls, with an average mean ratio of 2.65 (95% CI 1.59-4.43, P 5 0.009; Fig.…”

Section: Nfl In Ftdmentioning

confidence: 99%

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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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“…3D) [9,51,59,63]. The remaining study investigated 74 FTD cases compared with 17 MCI controls [9], with an NfL concentration ratio of 2.95 (95% CI 2.22–3.92; Fig. 3E).…”

Section: Resultsmentioning

confidence: 99%

Section: Nfl In Admentioning

confidence: 99%

Section: Nfl In Admentioning

confidence: 99%

Section: Nfl In Ftdmentioning

confidence: 99%

Section: Nfl In Ftdmentioning

confidence: 99%

See 3 more Smart Citations

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

View full text Add to dashboard Cite

show abstract

Serum neurofilament light chain in FTLD: association with C9orf72, clinical phenotype, and prognosis

Cajanus

Katisko

Kontkanen

et al. 2020

Ann Clin Transl Neurol

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ObjectiveThe aim of the present study was to compare the levels of serum neurofilament light chain (sNfL) in frontotemporal lobar degeneration (FTLD) patients of different clinical subtypes (bvFTD, PPA, and FTLD‐MND) and with or without the C9orf72 repeat expansion, and to correlate sNfL levels to disease progression, assessed by the brain atrophy rate and survival time.MethodsThe sNfL levels were determined from 78 FTLD patients (C9orf72 repeat expansion carriers [n = 26] and non‐carriers [n = 52]) with Single Molecule Array (SIMOA). The progression of brain atrophy was evaluated using repeated T1‐weighted MRI scans and the survival time from medical records.ResultsIn the total FTLD cohort, sNfL levels were significantly higher in C9orf72 repeat expansion carriers compared to non‐carriers. Considering clinical phenotypes, sNfL levels were higher in the C9orf72 repeat expansion carriers than in the non‐carriers in bvFTD and PPA groups. Furthermore, sNfL levels were the highest in the FTLD‐MND group (median 105 pg/mL) and the lowest in the bvFTD group (median 27 pg/mL). Higher sNfL levels significantly correlated with frontal cortical atrophy rate and subcortical grey matter atrophy rate. The higher sNfL levels also associated with shorter survival time.InterpretationOur results indicate that the C9orf72 repeat expansion carriers show elevated sNFL levels compared to non‐carriers and that the levels differ among different clinical phenotypes of FTLD. Higher sNfL levels correlated with a shorter survival time and cortical and subcortical atrophy rates. Thus, sNfL could prove as a potential prognostic biomarker in FTLD.

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Blood neurofilament light: a critical review of its application to neurologic disease

Barro

Chitnis

Weiner

2020

Ann Clin Transl Neurol

165

163

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Neuronal injury is a universal event that occurs in disease processes that affect both the central and peripheral nervous systems. A blood biomarker linked to neuronal injury would provide a critical measure to understand and treat neurologic diseases. Neurofilament light chain (NfL), a cytoskeletal protein expressed only in neurons, has emerged as such a biomarker. With the ability to quantify neuronal damage in blood, NfL is being applied to a wide range of neurologic conditions to investigate and monitor disease including assessment of treatment efficacy. Blood NfL is not specific for one disease and its release can also be induced by physiological processes. Longitudinal studies in multiple sclerosis, traumatic brain injury, and stroke show accumulation of NfL over days followed by elevated levels over months. Therefore, it may be hard to determine with a single measurement when the peak of NfL is reached and when the levels are normalized. Nonetheless, measurement of blood NfL provides a new blood biomarker for neurologic diseases overcoming the invasiveness of CSF sampling that restricted NfL clinical application. In this review, we examine the use of blood NfL as a biologic test for neurologic disease.

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Serum neurofilament light chain in behavioral variant frontotemporal dementia

Abstract: This study provides Class III evidence that for patients with cognitive problems, serum NfL concentration discriminates bvFTD from other forms of dementia.

Cited by 98 publications

References 44 publications

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

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

Serum neurofilament light chain in FTLD: association with C9orf72, clinical phenotype, and prognosis

Blood neurofilament light: a critical review of its application to neurologic disease

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