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Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis
INTRODUCTION: Phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N‐terminal and mid‐region p‐tau181 and p‐tau217 fragments are available, but head‐to‐head comparison in clinical settings is lacking. METHODS:...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246793/ https://www.ncbi.nlm.nih.gov/pubmed/33252199 http://dx.doi.org/10.1002/alz.12236 |
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author | Karikari, Thomas K. Emeršič, Andreja Vrillon, Agathe Lantero‐Rodriguez, Juan Ashton, Nicholas J. Kramberger, Milica Gregorič Dumurgier, Julien Hourregue, Claire Čučnik, Saša Brinkmalm, Gunnar Rot, Uroš Zetterberg, Henrik Paquet, Claire Blennow, Kaj |
author_facet | Karikari, Thomas K. Emeršič, Andreja Vrillon, Agathe Lantero‐Rodriguez, Juan Ashton, Nicholas J. Kramberger, Milica Gregorič Dumurgier, Julien Hourregue, Claire Čučnik, Saša Brinkmalm, Gunnar Rot, Uroš Zetterberg, Henrik Paquet, Claire Blennow, Kaj |
author_sort | Karikari, Thomas K. |
collection | PubMed |
description | INTRODUCTION: Phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N‐terminal and mid‐region p‐tau181 and p‐tau217 fragments are available, but head‐to‐head comparison in clinical settings is lacking. METHODS: N‐terminal‐directed p‐tau217 (N‐p‐tau217), N‐terminal‐directed p‐tau181 (N‐p‐tau181), and standard mid‐region p‐tau181 (Mid‐p‐tau181) biomarkers in CSF were evaluated in three cohorts (n = 503) to assess diagnostic performance, concordance, and associations with amyloid beta (Aβ). RESULTS: CSF N‐p‐tau217 and N‐p‐tau181 had better concordance (88.2%) than either with Mid‐p‐tau181 (79.7%–82.7%). N‐p‐tau217 and N‐p‐tau181 were significantly increased in early mild cognitive impairment (MCI)‐AD (A+T–N–) without changes in Mid‐p‐tau181 until AD‐dementia. N‐p‐tau217 and N‐p‐tau181 identified Aβ pathophysiology (area under the curve [AUC] = 94.8%–97.1%) and distinguished MCI‐AD from non‐AD MCI (AUC = 82.6%–90.5%) signficantly better than Mid‐p‐tau181 (AUC = 91.2% and 70.6%, respectively). P‐tau biomarkers equally differentiated AD from non‐AD dementia (AUC = 99.1%–99.8%). DISCUSSION: N‐p‐tau217 and N‐p‐tau181 could improve diagnostic accuracy in prodromal‐AD and clinical trial recruitment as both identify Aβ pathophysiology and differentiate early MCI‐AD better than Mid‐p‐tau181. |
format | Online Article Text |
id | pubmed-8246793 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-82467932021-07-02 Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis Karikari, Thomas K. Emeršič, Andreja Vrillon, Agathe Lantero‐Rodriguez, Juan Ashton, Nicholas J. Kramberger, Milica Gregorič Dumurgier, Julien Hourregue, Claire Čučnik, Saša Brinkmalm, Gunnar Rot, Uroš Zetterberg, Henrik Paquet, Claire Blennow, Kaj Alzheimers Dement Featured Articles INTRODUCTION: Phosphorylated tau (p‐tau) in cerebrospinal fluid (CSF) is an established Alzheimer's disease (AD) biomarker. Novel immunoassays targeting N‐terminal and mid‐region p‐tau181 and p‐tau217 fragments are available, but head‐to‐head comparison in clinical settings is lacking. METHODS: N‐terminal‐directed p‐tau217 (N‐p‐tau217), N‐terminal‐directed p‐tau181 (N‐p‐tau181), and standard mid‐region p‐tau181 (Mid‐p‐tau181) biomarkers in CSF were evaluated in three cohorts (n = 503) to assess diagnostic performance, concordance, and associations with amyloid beta (Aβ). RESULTS: CSF N‐p‐tau217 and N‐p‐tau181 had better concordance (88.2%) than either with Mid‐p‐tau181 (79.7%–82.7%). N‐p‐tau217 and N‐p‐tau181 were significantly increased in early mild cognitive impairment (MCI)‐AD (A+T–N–) without changes in Mid‐p‐tau181 until AD‐dementia. N‐p‐tau217 and N‐p‐tau181 identified Aβ pathophysiology (area under the curve [AUC] = 94.8%–97.1%) and distinguished MCI‐AD from non‐AD MCI (AUC = 82.6%–90.5%) signficantly better than Mid‐p‐tau181 (AUC = 91.2% and 70.6%, respectively). P‐tau biomarkers equally differentiated AD from non‐AD dementia (AUC = 99.1%–99.8%). DISCUSSION: N‐p‐tau217 and N‐p‐tau181 could improve diagnostic accuracy in prodromal‐AD and clinical trial recruitment as both identify Aβ pathophysiology and differentiate early MCI‐AD better than Mid‐p‐tau181. John Wiley and Sons Inc. 2020-11-30 2021-05 /pmc/articles/PMC8246793/ /pubmed/33252199 http://dx.doi.org/10.1002/alz.12236 Text en © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
spellingShingle | Featured Articles Karikari, Thomas K. Emeršič, Andreja Vrillon, Agathe Lantero‐Rodriguez, Juan Ashton, Nicholas J. Kramberger, Milica Gregorič Dumurgier, Julien Hourregue, Claire Čučnik, Saša Brinkmalm, Gunnar Rot, Uroš Zetterberg, Henrik Paquet, Claire Blennow, Kaj Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis |
title | Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis |
title_full | Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis |
title_fullStr | Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis |
title_full_unstemmed | Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis |
title_short | Head‐to‐head comparison of clinical performance of CSF phospho‐tau T181 and T217 biomarkers for Alzheimer's disease diagnosis |
title_sort | head‐to‐head comparison of clinical performance of csf phospho‐tau t181 and t217 biomarkers for alzheimer's disease diagnosis |
topic | Featured Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246793/ https://www.ncbi.nlm.nih.gov/pubmed/33252199 http://dx.doi.org/10.1002/alz.12236 |
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