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Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease
Background: CSF total-tau (t-tau) became a standard cerebrospinal fluid biomarker in Alzheimer’s disease (AD). In parallel, extremely elevated levels were observed in Creutzfeldt-Jakob disease (CJD). Therefore, tau is also considered as an alternative CJD biomarker, potentially complicating the inte...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874601/ https://www.ncbi.nlm.nih.gov/pubmed/35215868 http://dx.doi.org/10.3390/v14020276 |
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author | Hermann, Peter Haller, Philip Goebel, Stefan Bunck, Timothy Schmidt, Christian Wiltfang, Jens Zerr, Inga |
author_facet | Hermann, Peter Haller, Philip Goebel, Stefan Bunck, Timothy Schmidt, Christian Wiltfang, Jens Zerr, Inga |
author_sort | Hermann, Peter |
collection | PubMed |
description | Background: CSF total-tau (t-tau) became a standard cerebrospinal fluid biomarker in Alzheimer’s disease (AD). In parallel, extremely elevated levels were observed in Creutzfeldt-Jakob disease (CJD). Therefore, tau is also considered as an alternative CJD biomarker, potentially complicating the interpretation of results. We investigated CSF t-tau and the t-tau/phosphorylated tau181 ratio in the differential diagnosis of sCJD and rapidly-progressive AD (rpAD). In addition, high t-tau concentrations and associated tau-ratios were explored in an unselected laboratory cohort. Methods: Retrospective analyses included n = 310 patients with CJD (n = 205), non-rpAD (n = 65), and rpAD (n = 40). The diagnostic accuracies of biomarkers were calculated and compared. Differential diagnoses were evaluated in patients from a neurochemistry laboratory with CSF t-tau >1250 pg/mL (n = 199 out of 7036). Results: CSF t-tau showed an AUC of 0.942 in the discrimination of sCJD from AD and 0.918 in the discrimination from rpAD. The tau ratio showed significantly higher AUCs (p < 0.001) of 0.992 versus non-rpAD and 0.990 versus rpAD. In the neurochemistry cohort, prion diseases accounted for only 25% of very high CSF t-tau values. High tau-ratios were observed in CJD, but also in non-neurodegenerative diseases. Conclusions: CSF t-tau is a reliable biomarker for sCJD, but false positive results may occur, especially in rpAD and acute encephalopathies. The t-tau/p-tau ratio may improve the diagnostic accuracy in centers where specific biomarkers are not available. |
format | Online Article Text |
id | pubmed-8874601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88746012022-02-26 Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease Hermann, Peter Haller, Philip Goebel, Stefan Bunck, Timothy Schmidt, Christian Wiltfang, Jens Zerr, Inga Viruses Article Background: CSF total-tau (t-tau) became a standard cerebrospinal fluid biomarker in Alzheimer’s disease (AD). In parallel, extremely elevated levels were observed in Creutzfeldt-Jakob disease (CJD). Therefore, tau is also considered as an alternative CJD biomarker, potentially complicating the interpretation of results. We investigated CSF t-tau and the t-tau/phosphorylated tau181 ratio in the differential diagnosis of sCJD and rapidly-progressive AD (rpAD). In addition, high t-tau concentrations and associated tau-ratios were explored in an unselected laboratory cohort. Methods: Retrospective analyses included n = 310 patients with CJD (n = 205), non-rpAD (n = 65), and rpAD (n = 40). The diagnostic accuracies of biomarkers were calculated and compared. Differential diagnoses were evaluated in patients from a neurochemistry laboratory with CSF t-tau >1250 pg/mL (n = 199 out of 7036). Results: CSF t-tau showed an AUC of 0.942 in the discrimination of sCJD from AD and 0.918 in the discrimination from rpAD. The tau ratio showed significantly higher AUCs (p < 0.001) of 0.992 versus non-rpAD and 0.990 versus rpAD. In the neurochemistry cohort, prion diseases accounted for only 25% of very high CSF t-tau values. High tau-ratios were observed in CJD, but also in non-neurodegenerative diseases. Conclusions: CSF t-tau is a reliable biomarker for sCJD, but false positive results may occur, especially in rpAD and acute encephalopathies. The t-tau/p-tau ratio may improve the diagnostic accuracy in centers where specific biomarkers are not available. MDPI 2022-01-28 /pmc/articles/PMC8874601/ /pubmed/35215868 http://dx.doi.org/10.3390/v14020276 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hermann, Peter Haller, Philip Goebel, Stefan Bunck, Timothy Schmidt, Christian Wiltfang, Jens Zerr, Inga Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease |
title | Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease |
title_full | Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease |
title_fullStr | Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease |
title_full_unstemmed | Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease |
title_short | Total and Phosphorylated Cerebrospinal Fluid Tau in the Differential Diagnosis of Sporadic Creutzfeldt-Jakob Disease and Rapidly Progressive Alzheimer’s Disease |
title_sort | total and phosphorylated cerebrospinal fluid tau in the differential diagnosis of sporadic creutzfeldt-jakob disease and rapidly progressive alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8874601/ https://www.ncbi.nlm.nih.gov/pubmed/35215868 http://dx.doi.org/10.3390/v14020276 |
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