期刊
ALZHEIMERS RESEARCH & THERAPY
卷 13, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s13195-021-00815-6
关键词
Dementia; Creutzfeldt-Jakob disease; Biomarkers; Plasma; Neurofilament light; Tau; Diagnosis; Disease progression
资金
- Instituto Carlos III [PI19/00144]
- Robert Koch Institute through the Federal Ministry of Health [1369-341]
- Fondo Europeo de Desarrollo Regional (FEDER) through the Interreg V-A Espana-Francia-Andorra (POCTEFA 2014-2020 programme)
- Ministry of Business and Knowledge of the Government of Catalonia [2018-BP-00129]
- EU Horizon 2020 programme under an MSCA grant agreement [801370]
- Swedish Research Council [2018-02532, 2017-00915]
- European Research Council [681712]
- Swedish State Support for Clinical Research [ALFGBG-720931]
- Alzheimer Drug Discovery Foundation (ADDF), USA [201809-2016862, RDAPB-201809-2016615]
- UK Dementia Research Institute at UCL
- Swedish Alzheimer Foundation [AF-742881]
- Hjarnfonden, Sweden [FO2017-0243]
- Swedish government [ALFGBG-715986]
- European Union Joint Program for Neurodegenerative Disorders [JPND2019-466-236]
- Swedish government
This study aimed to determine the accuracy of plasma Nfl and t-tau in the differential diagnosis of neurodegenerative dementias and their potential value as prognostic markers. Results showed that Nfl and t-tau could differentiate different neurological conditions, with t-tau being associated with disease duration.
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.
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