Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up

Abstract Various proteins play a decisive role in the pathology of different neurodegenerative diseases. Nonetheless, most of these proteins can only be detected during a neuropathological assessment, although some non-specific biomarkers are routinely tested for in the cerebrospinal fluid (CSF) as...

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Autores principales:	Magdalena Bruzova, Robert Rusina, Zuzana Stejskalova, Radoslav Matej
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/de857d9a05f547e2872766e12499d608
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spelling	oai:doaj.org-article:de857d9a05f547e2872766e12499d6082021-12-02T15:49:31ZAutopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up10.1038/s41598-021-90366-52045-2322https://doaj.org/article/de857d9a05f547e2872766e12499d6082021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90366-5https://doaj.org/toc/2045-2322Abstract Various proteins play a decisive role in the pathology of different neurodegenerative diseases. Nonetheless, most of these proteins can only be detected during a neuropathological assessment, although some non-specific biomarkers are routinely tested for in the cerebrospinal fluid (CSF) as a part of the differential diagnosis of dementia. In antemortem CSF samples from 117 patients with different types of neuropathologically confirmed neurodegenerative disease with dementia, we assessed total-tau (t-tau), phosphorylated-tau (181P) (p-tau), amyloid-beta (1–42) (Aβ42), TAR DNA binding protein (TDP)-43, progranulin (PGRN), and neurofilament light (NfL) chain levels, and positivity of protein 14-3-3. We found t-tau levels and the t-tau/p-tau ratios were significantly higher in prion diseases compared to the other neurodegenerative diseases. Statistically significant differences in the t-tau/Aβ42 ratio predominantly corresponded to t-tau levels in prion diseases and Aβ42 levels in AD. TDP-43 levels were significantly lower in prion diseases. Additionally, the TDP-43/Aβ42 ratio was better able to distinguish Alzheimer’s disease from other neurodegenerative diseases compared to using Aβ42 alone. In frontotemporal lobar degeneration, PRGN levels were significantly higher in comparison to other neurodegenerative diseases. There is an increasing need for biomarkers suitable for diagnostic workups for neurodegenerative diseases. It appears that adding TDP-43 and PGRN to the testing panel for neurodegenerative diseases could improve the resolution of differential diagnoses.Magdalena BruzovaRobert RusinaZuzana StejskalovaRadoslav MatejNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Magdalena Bruzova Robert Rusina Zuzana Stejskalova Radoslav Matej Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
description	Abstract Various proteins play a decisive role in the pathology of different neurodegenerative diseases. Nonetheless, most of these proteins can only be detected during a neuropathological assessment, although some non-specific biomarkers are routinely tested for in the cerebrospinal fluid (CSF) as a part of the differential diagnosis of dementia. In antemortem CSF samples from 117 patients with different types of neuropathologically confirmed neurodegenerative disease with dementia, we assessed total-tau (t-tau), phosphorylated-tau (181P) (p-tau), amyloid-beta (1–42) (Aβ42), TAR DNA binding protein (TDP)-43, progranulin (PGRN), and neurofilament light (NfL) chain levels, and positivity of protein 14-3-3. We found t-tau levels and the t-tau/p-tau ratios were significantly higher in prion diseases compared to the other neurodegenerative diseases. Statistically significant differences in the t-tau/Aβ42 ratio predominantly corresponded to t-tau levels in prion diseases and Aβ42 levels in AD. TDP-43 levels were significantly lower in prion diseases. Additionally, the TDP-43/Aβ42 ratio was better able to distinguish Alzheimer’s disease from other neurodegenerative diseases compared to using Aβ42 alone. In frontotemporal lobar degeneration, PRGN levels were significantly higher in comparison to other neurodegenerative diseases. There is an increasing need for biomarkers suitable for diagnostic workups for neurodegenerative diseases. It appears that adding TDP-43 and PGRN to the testing panel for neurodegenerative diseases could improve the resolution of differential diagnoses.
format	article
author	Magdalena Bruzova Robert Rusina Zuzana Stejskalova Radoslav Matej
author_facet	Magdalena Bruzova Robert Rusina Zuzana Stejskalova Radoslav Matej
author_sort	Magdalena Bruzova
title	Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
title_short	Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
title_full	Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
title_fullStr	Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
title_full_unstemmed	Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
title_sort	autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/de857d9a05f547e2872766e12499d608
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Autopsy-diagnosed neurodegenerative dementia cases support the use of cerebrospinal fluid protein biomarkers in the diagnostic work-up

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