C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease

Abstract This study assesses whether C-terminal fragments (CTF) of the amyloid precursor protein (APP) are present in cerebrospinal fluid (CSF) and their potential as biomarkers for Alzheimer’s disease (AD). Immunoprecipitation and simultaneous assay by Western blotting using multiplex fluorescence...

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Autores principales:	María-Salud García-Ayllón, Inmaculada Lopez-Font, Claudia P. Boix, Juan Fortea, Raquel Sánchez-Valle, Alberto Lleó, José-Luis Molinuevo, Henrik Zetterberg, Kaj Blennow, Javier Sáez-Valero
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cb69aef9120f49b8950c4c51cc31dc80
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spelling	oai:doaj.org-article:cb69aef9120f49b8950c4c51cc31dc802021-12-02T12:32:44ZC-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease10.1038/s41598-017-02841-72045-2322https://doaj.org/article/cb69aef9120f49b8950c4c51cc31dc802017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02841-7https://doaj.org/toc/2045-2322Abstract This study assesses whether C-terminal fragments (CTF) of the amyloid precursor protein (APP) are present in cerebrospinal fluid (CSF) and their potential as biomarkers for Alzheimer’s disease (AD). Immunoprecipitation and simultaneous assay by Western blotting using multiplex fluorescence imaging with specific antibodies against particular domains served to characterize CTFs of APP in human CSF. We demonstrate that APP-CTFs are detectable in human CSF, being the most abundant a 25-kDa fragment, probably resulting from proteolytic processing by η-secretase. The level of the 25-kDa APP-CTF was evaluated in three independent CSF sample sets of patients and controls. The CSF level of this 25-kDa CTF is higher in subjects with autosomal dominant AD linked to PSEN1 mutations, in demented Down syndrome individuals and in sporadic AD subjects compared to age-matched controls. Our data suggest that APP-CTF could be a potential diagnostic biomarker for AD.María-Salud García-AyllónInmaculada Lopez-FontClaudia P. BoixJuan ForteaRaquel Sánchez-ValleAlberto LleóJosé-Luis MolinuevoHenrik ZetterbergKaj BlennowJavier Sáez-ValeroNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q María-Salud García-Ayllón Inmaculada Lopez-Font Claudia P. Boix Juan Fortea Raquel Sánchez-Valle Alberto Lleó José-Luis Molinuevo Henrik Zetterberg Kaj Blennow Javier Sáez-Valero C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease
description	Abstract This study assesses whether C-terminal fragments (CTF) of the amyloid precursor protein (APP) are present in cerebrospinal fluid (CSF) and their potential as biomarkers for Alzheimer’s disease (AD). Immunoprecipitation and simultaneous assay by Western blotting using multiplex fluorescence imaging with specific antibodies against particular domains served to characterize CTFs of APP in human CSF. We demonstrate that APP-CTFs are detectable in human CSF, being the most abundant a 25-kDa fragment, probably resulting from proteolytic processing by η-secretase. The level of the 25-kDa APP-CTF was evaluated in three independent CSF sample sets of patients and controls. The CSF level of this 25-kDa CTF is higher in subjects with autosomal dominant AD linked to PSEN1 mutations, in demented Down syndrome individuals and in sporadic AD subjects compared to age-matched controls. Our data suggest that APP-CTF could be a potential diagnostic biomarker for AD.
format	article
author	María-Salud García-Ayllón Inmaculada Lopez-Font Claudia P. Boix Juan Fortea Raquel Sánchez-Valle Alberto Lleó José-Luis Molinuevo Henrik Zetterberg Kaj Blennow Javier Sáez-Valero
author_facet	María-Salud García-Ayllón Inmaculada Lopez-Font Claudia P. Boix Juan Fortea Raquel Sánchez-Valle Alberto Lleó José-Luis Molinuevo Henrik Zetterberg Kaj Blennow Javier Sáez-Valero
author_sort	María-Salud García-Ayllón
title	C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease
title_short	C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease
title_full	C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease
title_fullStr	C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease
title_full_unstemmed	C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease
title_sort	c-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for alzheimer disease
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/cb69aef9120f49b8950c4c51cc31dc80
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C-terminal fragments of the amyloid precursor protein in cerebrospinal fluid as potential biomarkers for Alzheimer disease

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