Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease
Abstract Background Blood neurofilament light (Nfl) and total-tau (t-tau) have been described to be increased in several neurological conditions, including prion diseases and other neurodegenerative dementias. Here, we aim to determine the accuracy of plasma Nfl and t-tau in the differential diagnos...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2021-04-01
|
Series: | Alzheimer’s Research & Therapy |
Subjects: | |
Online Access: | https://doi.org/10.1186/s13195-021-00815-6 |
id |
doaj-6ecc23b919cc44e09920260ce6e6d546 |
---|---|
record_format |
Article |
spelling |
doaj-6ecc23b919cc44e09920260ce6e6d5462021-04-25T11:45:14ZengBMCAlzheimer’s Research & Therapy1758-91932021-04-0113111510.1186/s13195-021-00815-6Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob diseaseInga Zerr0Anna Villar-Piqué1Peter Hermann2Matthias Schmitz3Daniela Varges4Isidre Ferrer5Joachim Riggert6Henrik Zetterberg7Kaj Blennow8Franc Llorens9Department of Neurology, National Reference Center for TSE Surveillance, University Medical CenterCenter for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), L’Hospitalet de LlobregatDepartment of Neurology, National Reference Center for TSE Surveillance, University Medical CenterDepartment of Neurology, National Reference Center for TSE Surveillance, University Medical CenterDepartment of Neurology, National Reference Center for TSE Surveillance, University Medical CenterCenter for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED), L’Hospitalet de LlobregatDepartment of Transfusion Medicine, University Medical SchoolDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of GothenburgDepartment of Neurology, National Reference Center for TSE Surveillance, University Medical CenterAbstract Background Blood neurofilament light (Nfl) and total-tau (t-tau) have been described to be increased in several neurological conditions, including prion diseases and other neurodegenerative dementias. Here, we aim to determine the accuracy of plasma Nfl and t-tau in the differential diagnosis of neurodegenerative dementias and their potential value as prognostic markers of disease severity. Methods Plasma Nfl and t-tau were measured in healthy controls (HC, n = 70), non-neurodegenerative neurological disease with (NND-Dem, n = 17) and without dementia syndrome (NND, n = 26), Alzheimer’s disease (AD, n = 44), Creutzfeldt-Jakob disease (CJD, n = 83), dementia with Lewy bodies/Parkinson’s disease with dementia (DLB/PDD, n = 35), frontotemporal dementia (FTD, n = 12), and vascular dementia (VaD, n = 22). Biomarker diagnostic accuracies and cutoff points for the diagnosis of CJD were calculated, and associations between Nfl and t-tau concentrations with other fluid biomarkers, demographic, genetic, and clinical data in CJD cases were assessed. Additionally, the value of Nfl and t-tau predicting disease survival in CJD was evaluated. Results Among diagnostic groups, highest plasma Nfl and t-tau concentrations were detected in CJD (fold changes of 38 and 18, respectively, compared to HC). Elevated t-tau was able to differentiate CJD from all other groups, whereas elevated Nfl concentrations were also detected in NND-Dem, AD, DLB/PDD, FTD, and VaD compared to HC. Both biomarkers discriminated CJD from non-CJD dementias with an AUC of 0.93. In CJD, plasma t-tau, but not Nfl, was associated with PRNP codon 129 genotype and CJD subtype. Positive correlations were observed between plasma Nfl and t-tau concentrations, as well as between plasma and CSF concentrations of both biomarkers (p < 0.001). Nfl was increased in rapidly progressive AD (rpAD) compared to slow progressive AD (spAD) and associated to Mini-Mental State Examination results. However, Nfl displayed higher accuracy than t-tau discriminating CJD from rpAD and spAD. Finally, plasma t-tau, but not plasma Nfl, was significantly associated with disease duration, offering a moderate survival prediction capacity. Conclusions Plasma Nfl and t-tau are useful complementary biomarkers for the differential diagnosis of CJD. Additionally, plasma t-tau emerges as a potential prognostic marker of disease duration.https://doi.org/10.1186/s13195-021-00815-6DementiaCreutzfeldt-Jakob diseaseBiomarkersPlasmaNeurofilament lightTau |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Inga Zerr Anna Villar-Piqué Peter Hermann Matthias Schmitz Daniela Varges Isidre Ferrer Joachim Riggert Henrik Zetterberg Kaj Blennow Franc Llorens |
spellingShingle |
Inga Zerr Anna Villar-Piqué Peter Hermann Matthias Schmitz Daniela Varges Isidre Ferrer Joachim Riggert Henrik Zetterberg Kaj Blennow Franc Llorens Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease Alzheimer’s Research & Therapy Dementia Creutzfeldt-Jakob disease Biomarkers Plasma Neurofilament light Tau |
author_facet |
Inga Zerr Anna Villar-Piqué Peter Hermann Matthias Schmitz Daniela Varges Isidre Ferrer Joachim Riggert Henrik Zetterberg Kaj Blennow Franc Llorens |
author_sort |
Inga Zerr |
title |
Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease |
title_short |
Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease |
title_full |
Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease |
title_fullStr |
Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease |
title_full_unstemmed |
Diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic Creutzfeldt-Jakob disease |
title_sort |
diagnostic and prognostic value of plasma neurofilament light and total-tau in sporadic creutzfeldt-jakob disease |
publisher |
BMC |
series |
Alzheimer’s Research & Therapy |
issn |
1758-9193 |
publishDate |
2021-04-01 |
description |
Abstract Background Blood neurofilament light (Nfl) and total-tau (t-tau) have been described to be increased in several neurological conditions, including prion diseases and other neurodegenerative dementias. Here, we aim to determine the accuracy of plasma Nfl and t-tau in the differential diagnosis of neurodegenerative dementias and their potential value as prognostic markers of disease severity. Methods Plasma Nfl and t-tau were measured in healthy controls (HC, n = 70), non-neurodegenerative neurological disease with (NND-Dem, n = 17) and without dementia syndrome (NND, n = 26), Alzheimer’s disease (AD, n = 44), Creutzfeldt-Jakob disease (CJD, n = 83), dementia with Lewy bodies/Parkinson’s disease with dementia (DLB/PDD, n = 35), frontotemporal dementia (FTD, n = 12), and vascular dementia (VaD, n = 22). Biomarker diagnostic accuracies and cutoff points for the diagnosis of CJD were calculated, and associations between Nfl and t-tau concentrations with other fluid biomarkers, demographic, genetic, and clinical data in CJD cases were assessed. Additionally, the value of Nfl and t-tau predicting disease survival in CJD was evaluated. Results Among diagnostic groups, highest plasma Nfl and t-tau concentrations were detected in CJD (fold changes of 38 and 18, respectively, compared to HC). Elevated t-tau was able to differentiate CJD from all other groups, whereas elevated Nfl concentrations were also detected in NND-Dem, AD, DLB/PDD, FTD, and VaD compared to HC. Both biomarkers discriminated CJD from non-CJD dementias with an AUC of 0.93. In CJD, plasma t-tau, but not Nfl, was associated with PRNP codon 129 genotype and CJD subtype. Positive correlations were observed between plasma Nfl and t-tau concentrations, as well as between plasma and CSF concentrations of both biomarkers (p < 0.001). Nfl was increased in rapidly progressive AD (rpAD) compared to slow progressive AD (spAD) and associated to Mini-Mental State Examination results. However, Nfl displayed higher accuracy than t-tau discriminating CJD from rpAD and spAD. Finally, plasma t-tau, but not plasma Nfl, was significantly associated with disease duration, offering a moderate survival prediction capacity. Conclusions Plasma Nfl and t-tau are useful complementary biomarkers for the differential diagnosis of CJD. Additionally, plasma t-tau emerges as a potential prognostic marker of disease duration. |
topic |
Dementia Creutzfeldt-Jakob disease Biomarkers Plasma Neurofilament light Tau |
url |
https://doi.org/10.1186/s13195-021-00815-6 |
work_keys_str_mv |
AT ingazerr diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT annavillarpique diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT peterhermann diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT matthiasschmitz diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT danielavarges diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT isidreferrer diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT joachimriggert diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT henrikzetterberg diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT kajblennow diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease AT francllorens diagnosticandprognosticvalueofplasmaneurofilamentlightandtotaltauinsporadiccreutzfeldtjakobdisease |
_version_ |
1721509464839815168 |