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Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics

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Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics. / Kojima, Y.; Kasai, T.; Noto, Y.-I. et al.
In: PLoS ONE, Vol. 16, No. 11 , e0260323, 29.11.2021.

Research output: Contribution to Journal/MagazineJournal articlepeer-review

Harvard

Kojima, Y, Kasai, T, Noto, Y-I, Ohmichi, T, Tatebe, H, Kitaoji, T, Tsuji, Y, Kitani-Morii, F, Shinomoto, M, Allsop, D, Teramukai, S, Mizuno, T & Tokuda, T 2021, 'Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics', PLoS ONE, vol. 16, no. 11 , e0260323. https://doi.org/10.1371/journal.pone.0260323

APA

Kojima, Y., Kasai, T., Noto, Y.-I., Ohmichi, T., Tatebe, H., Kitaoji, T., Tsuji, Y., Kitani-Morii, F., Shinomoto, M., Allsop, D., Teramukai, S., Mizuno, T., & Tokuda, T. (2021). Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics. PLoS ONE, 16(11 ), Article e0260323. https://doi.org/10.1371/journal.pone.0260323

Vancouver

Kojima Y, Kasai T, Noto YI, Ohmichi T, Tatebe H, Kitaoji T et al. Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics. PLoS ONE. 2021 Nov 29;16(11 ):e0260323. doi: 10.1371/journal.pone.0260323

Author

Kojima, Y. ; Kasai, T. ; Noto, Y.-I. et al. / Amyotrophic lateral sclerosis : Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics. In: PLoS ONE. 2021 ; Vol. 16, No. 11 .

Bibtex

@article{c7cad986fda44973a68f69c8c10c1b03,
title = "Amyotrophic lateral sclerosis: Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics",
abstract = "Objectives We previously reported the diagnostic and prognostic performance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma as amyotrophic lateral sclerosis (ALS) biomarkers. The present study aimed to elucidate associations between clinical characteristics and the markers as well as mutual associations of the markers in ALS patients using the same dataset. Methods NfL, TDP-43, and t-tau levels in CSF and plasma in 75 ALS patients were analyzed. The associations between those markers and clinical details were investigated by uni- and multivariate analyses. Correlations between the markers were analyzed univariately. Results In multivariate analysis of CSF proteins, the disease progression rate (DPR) was positively correlated with NfL (β: 0.51, p = 0.007) and t-tau (β: 0.37, p = 0.03). Plasma NfL was correlated with age (β: 0.53, p = 0.005) and diagnostic grade (β: -0.42, p = 0.02) in multivariate analysis. Plasma TDP-43 was correlated negatively with split hand index (β: -0.48, p = 0.04) and positively with % vital capacity (β: 0.64, p = 0.03) in multivariate analysis. Regarding mutual biomarker analysis, a negative correlation between CSF-NfL and TDP-43 was identified (r: -0.36, p = 0.002). Conclusions Elevated NfL and t-tau levels in CSF may be biomarkers to predict rapid DPR from onset to sample collection. The negative relationship between CSF NfL and TDP-43 suggests that elevation of CSF TDP-43 in ALS is not a simple consequence of its release into CSF during neurodegeneration. The negative correlation between plasma TDP-43 and split hand index may support the pathophysiological association between plasma TDP-43 and ALS. ",
keywords = "biological marker, neurofilament light chain, neurofilament protein, TAR DNA binding protein, tau protein, unclassified drug, adult, age, aged, amyotrophic lateral sclerosis, Article, blood analysis, cerebrospinal fluid analysis, clinical feature, cohort analysis, correlation analysis, disease association, disease course, ectrodactyly, female, human, major clinical study, male, middle aged, multivariate analysis, nerve degeneration, pathophysiology, prediction, protein secretion, univariate analysis, vital capacity",
author = "Y. Kojima and T. Kasai and Y.-I. Noto and T. Ohmichi and H. Tatebe and T. Kitaoji and Y. Tsuji and F. Kitani-Morii and M. Shinomoto and D. Allsop and S. Teramukai and T. Mizuno and T. Tokuda",
year = "2021",
month = nov,
day = "29",
doi = "10.1371/journal.pone.0260323",
language = "English",
volume = "16",
journal = "PLoS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "11 ",

}

RIS

TY - JOUR

T1 - Amyotrophic lateral sclerosis

T2 - Correlations between fluid biomarkers of NfL, TDP-43, and tau, and clinical characteristics

AU - Kojima, Y.

AU - Kasai, T.

AU - Noto, Y.-I.

AU - Ohmichi, T.

AU - Tatebe, H.

AU - Kitaoji, T.

AU - Tsuji, Y.

AU - Kitani-Morii, F.

AU - Shinomoto, M.

AU - Allsop, D.

AU - Teramukai, S.

AU - Mizuno, T.

AU - Tokuda, T.

PY - 2021/11/29

Y1 - 2021/11/29

N2 - Objectives We previously reported the diagnostic and prognostic performance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma as amyotrophic lateral sclerosis (ALS) biomarkers. The present study aimed to elucidate associations between clinical characteristics and the markers as well as mutual associations of the markers in ALS patients using the same dataset. Methods NfL, TDP-43, and t-tau levels in CSF and plasma in 75 ALS patients were analyzed. The associations between those markers and clinical details were investigated by uni- and multivariate analyses. Correlations between the markers were analyzed univariately. Results In multivariate analysis of CSF proteins, the disease progression rate (DPR) was positively correlated with NfL (β: 0.51, p = 0.007) and t-tau (β: 0.37, p = 0.03). Plasma NfL was correlated with age (β: 0.53, p = 0.005) and diagnostic grade (β: -0.42, p = 0.02) in multivariate analysis. Plasma TDP-43 was correlated negatively with split hand index (β: -0.48, p = 0.04) and positively with % vital capacity (β: 0.64, p = 0.03) in multivariate analysis. Regarding mutual biomarker analysis, a negative correlation between CSF-NfL and TDP-43 was identified (r: -0.36, p = 0.002). Conclusions Elevated NfL and t-tau levels in CSF may be biomarkers to predict rapid DPR from onset to sample collection. The negative relationship between CSF NfL and TDP-43 suggests that elevation of CSF TDP-43 in ALS is not a simple consequence of its release into CSF during neurodegeneration. The negative correlation between plasma TDP-43 and split hand index may support the pathophysiological association between plasma TDP-43 and ALS.

AB - Objectives We previously reported the diagnostic and prognostic performance of neurofilament light chain (NfL), TAR DNA-binding protein 43 (TDP-43), and total tau (t-tau) in cerebrospinal fluid (CSF) and plasma as amyotrophic lateral sclerosis (ALS) biomarkers. The present study aimed to elucidate associations between clinical characteristics and the markers as well as mutual associations of the markers in ALS patients using the same dataset. Methods NfL, TDP-43, and t-tau levels in CSF and plasma in 75 ALS patients were analyzed. The associations between those markers and clinical details were investigated by uni- and multivariate analyses. Correlations between the markers were analyzed univariately. Results In multivariate analysis of CSF proteins, the disease progression rate (DPR) was positively correlated with NfL (β: 0.51, p = 0.007) and t-tau (β: 0.37, p = 0.03). Plasma NfL was correlated with age (β: 0.53, p = 0.005) and diagnostic grade (β: -0.42, p = 0.02) in multivariate analysis. Plasma TDP-43 was correlated negatively with split hand index (β: -0.48, p = 0.04) and positively with % vital capacity (β: 0.64, p = 0.03) in multivariate analysis. Regarding mutual biomarker analysis, a negative correlation between CSF-NfL and TDP-43 was identified (r: -0.36, p = 0.002). Conclusions Elevated NfL and t-tau levels in CSF may be biomarkers to predict rapid DPR from onset to sample collection. The negative relationship between CSF NfL and TDP-43 suggests that elevation of CSF TDP-43 in ALS is not a simple consequence of its release into CSF during neurodegeneration. The negative correlation between plasma TDP-43 and split hand index may support the pathophysiological association between plasma TDP-43 and ALS.

KW - biological marker

KW - neurofilament light chain

KW - neurofilament protein

KW - TAR DNA binding protein

KW - tau protein

KW - unclassified drug

KW - adult

KW - age

KW - aged

KW - amyotrophic lateral sclerosis

KW - Article

KW - blood analysis

KW - cerebrospinal fluid analysis

KW - clinical feature

KW - cohort analysis

KW - correlation analysis

KW - disease association

KW - disease course

KW - ectrodactyly

KW - female

KW - human

KW - major clinical study

KW - male

KW - middle aged

KW - multivariate analysis

KW - nerve degeneration

KW - pathophysiology

KW - prediction

KW - protein secretion

KW - univariate analysis

KW - vital capacity

U2 - 10.1371/journal.pone.0260323

DO - 10.1371/journal.pone.0260323

M3 - Journal article

VL - 16

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

IS - 11

M1 - e0260323

ER -