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Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS: A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau

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Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS : A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau. / Kasai, Takashi; Kojima, Yuta; Ohmichi, Takuma; Tatebe, Harutsugu; Tsuji, Yukiko; Noto, Yu-ichi; Kitani-Morii, Fukiko; Shinomoto, Makiko; Allsop, David; Mizuno, Toshiki; Tokuda, Takahiko.

In: Annals of Clinical and Translational Neurology, Vol. 6, No. 12, 01.12.2019, p. 2489-2502.

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Kasai, T, Kojima, Y, Ohmichi, T, Tatebe, H, Tsuji, Y, Noto, Y, Kitani-Morii, F, Shinomoto, M, Allsop, D, Mizuno, T & Tokuda, T 2019, 'Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS: A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau', Annals of Clinical and Translational Neurology, vol. 6, no. 12, pp. 2489-2502. https://doi.org/10.1002/acn3.50943

APA

Kasai, T., Kojima, Y., Ohmichi, T., Tatebe, H., Tsuji, Y., Noto, Y., Kitani-Morii, F., Shinomoto, M., Allsop, D., Mizuno, T., & Tokuda, T. (2019). Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS: A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau. Annals of Clinical and Translational Neurology, 6(12), 2489-2502. https://doi.org/10.1002/acn3.50943

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Kasai, Takashi ; Kojima, Yuta ; Ohmichi, Takuma ; Tatebe, Harutsugu ; Tsuji, Yukiko ; Noto, Yu-ichi ; Kitani-Morii, Fukiko ; Shinomoto, Makiko ; Allsop, David ; Mizuno, Toshiki ; Tokuda, Takahiko. / Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS : A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau. In: Annals of Clinical and Translational Neurology. 2019 ; Vol. 6, No. 12. pp. 2489-2502.

Bibtex

@article{2129222de2d6469e9db8340e335c13c8,
title = "Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS: A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau",
abstract = "Objective To determine the diagnostic and prognostic significance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods This was a single-center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age-matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not age-matched) patients with motor weakness resulting from neuromuscular diseases. NfL, TDP-43, and t-tau levels in CSF and plasma were measured using ultrasensitive single molecule assay (Simoa) technology. Results The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP-43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NfL. When the CSF NfL and CSF TDP-43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP-43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP-43 may be a useful biomarker for the diagnosis of ALS. ",
author = "Takashi Kasai and Yuta Kojima and Takuma Ohmichi and Harutsugu Tatebe and Yukiko Tsuji and Yu-ichi Noto and Fukiko Kitani-Morii and Makiko Shinomoto and David Allsop and Toshiki Mizuno and Takahiko Tokuda",
year = "2019",
month = dec
day = "1",
doi = "10.1002/acn3.50943",
language = "English",
volume = "6",
pages = "2489--2502",
journal = "Annals of Clinical and Translational Neurology",
issn = "2328-9503",
publisher = "John Wiley and Sons Ltd",
number = "12",

}

RIS

TY - JOUR

T1 - Combined use of CSF NfL and CSF TDP-43 improves diagnostic performance in ALS

T2 - A comprehensive analysis on diagnostic and prognostic significance of plasma and CSF NfL, TDP-43, and tau

AU - Kasai, Takashi

AU - Kojima, Yuta

AU - Ohmichi, Takuma

AU - Tatebe, Harutsugu

AU - Tsuji, Yukiko

AU - Noto, Yu-ichi

AU - Kitani-Morii, Fukiko

AU - Shinomoto, Makiko

AU - Allsop, David

AU - Mizuno, Toshiki

AU - Tokuda, Takahiko

PY - 2019/12/1

Y1 - 2019/12/1

N2 - Objective To determine the diagnostic and prognostic significance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods This was a single-center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age-matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not age-matched) patients with motor weakness resulting from neuromuscular diseases. NfL, TDP-43, and t-tau levels in CSF and plasma were measured using ultrasensitive single molecule assay (Simoa) technology. Results The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP-43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NfL. When the CSF NfL and CSF TDP-43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP-43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP-43 may be a useful biomarker for the diagnosis of ALS.

AB - Objective To determine the diagnostic and prognostic significance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma of patients with amyotrophic lateral sclerosis (ALS) and to investigate whether the combined use of those biomarker candidates can improve their diagnostic performance. Methods This was a single-center, prospective, longitudinal study. CSF and plasma samples were collected at the time of enrollment from a discovery cohort of 29 patients with ALS and 29 age-matched controls without neurodegenerative disease. In a validation cohort, there were 46 patients with ALS, and 46 control (not age-matched) patients with motor weakness resulting from neuromuscular diseases. NfL, TDP-43, and t-tau levels in CSF and plasma were measured using ultrasensitive single molecule assay (Simoa) technology. Results The following findings were reproducibly observed among the discovery and validation cohorts: increased levels of CSF NfL, plasma NfL, and CSF TDP-43 in ALS compared with control groups; shorter survival associated with higher levels of CSF and plasma NfL. When the CSF NfL and CSF TDP-43 levels were combined, the areas under the ROC curves (AUC) were slightly improved relative to AUCs for each biomarker alone. Interpretation CSF and plasma NfL may not only serve as diagnostic biomarkers but also provide a measure of disease progression. CSF TDP-43 is also useful as a diagnostic biomarker of ALS, but has no prognostic value. The combined use of CSF NfL and CSF TDP-43 may be a useful biomarker for the diagnosis of ALS.

U2 - 10.1002/acn3.50943

DO - 10.1002/acn3.50943

M3 - Journal article

C2 - 31742901

VL - 6

SP - 2489

EP - 2502

JO - Annals of Clinical and Translational Neurology

JF - Annals of Clinical and Translational Neurology

SN - 2328-9503

IS - 12

ER -