Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples

Multielemental analysis of cerebrospinal fluid (CSF) yields critical insights into the pathophysiology of neurological disorders and holds potential as a diagnostic and predictive tool for Alzheimer's disease (AD). The present work presents the development and validation of an inductively coupl...

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Autores: Pérez-Ramírez, R, Cuchillo-Ibáñez, I, Sánchez-Romero, R, Beltrán-Sanahuja, A, Escamilla, S, Molina-Gasset, R, Zetterberg, H, Blennow, K, Sáez-Valero, J, Todolí-Torro, J
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Recursos:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
Repositorio:r-FISABIO. Repositorio Institucional de Producción Científica
OAI Identifier:oai:fisabio.fundanetsuite.com:p20219
Acesso em linha:https://fisabio.portalinvestigacion.com/publicaciones/20219
Access Level:acceso abierto
Palavra-chave:Alzheimer's disease
biomarker
chemical elements
CSF
ICP-MS/MS
Mn
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spelling Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease SamplesPérez-Ramírez, RCuchillo-Ibáñez, ISánchez-Romero, RBeltrán-Sanahuja, AEscamilla, SMolina-Gasset, RZetterberg, HBlennow, KSáez-Valero, JTodolí-Torro, JAlzheimer's diseasebiomarkerchemical elementsCSFICP-MS/MSMnMultielemental analysis of cerebrospinal fluid (CSF) yields critical insights into the pathophysiology of neurological disorders and holds potential as a diagnostic and predictive tool for Alzheimer's disease (AD). The present work presents the development and validation of an inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) based method for multielemental determination in CSF, including metals and metalloids as analytes. As a proof of concept, the importance of the CSF element determination was evaluated in a cohort of patients with AD (n = 20) and non-AD controls (n = 19) who displayed typical levels of core CSF biomarkers (A beta 42, P-tau, and total-tau). Discrete sample introduction ICP-MS/MS procedure was effective for accurate and precise CSF analysis. The methodology provided better sensitivities and limits of detection than a conventional one based on sample dilution and analysis in continuous sample introduction mode, while only requiring a 20 mu L CSF sample volume. A total of 24 elements were encountered and quantified in CSF, with reduced levels of Mn, Cr, Se, Fe, and Zn in the CSF from AD patients and increased levels of Ag and Bi, compared with non-AD patients. Particularly, Mn fully discriminated AD from non-AD subjects, with binary regression analysis indicating that Mn was the most effective element to distinguish between AD and non-AD groups. Furthermore, distinctive correlation profiles were found between AD and non-AD controls for elements with AD core biomarkers and the alternative amyloidogenic sAPP beta fragment. Quantitative determination of metals, metalloids and non-metals displays differences associated with pathological status, serving as additional biomarkers for neurological diseases.Blackwell Publishing Inc.2025info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fisabio.portalinvestigacion.com/publicaciones/20219JOURNAL OF NEUROCHEMISTRYISSN: 14714159ISSNe: 00223042reponame:r-FISABIO. Repositorio Institucional de Producción Científicainstname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)Inglésinfo:eu-repo/semantics/openAccessoai:fisabio.fundanetsuite.com:p202192026-06-11T12:45:17Z
dc.title.none.fl_str_mv Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
title Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
spellingShingle Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
Pérez-Ramírez, R
Alzheimer's disease
biomarker
chemical elements
CSF
ICP-MS/MS
Mn
title_short Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
title_full Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
title_fullStr Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
title_full_unstemmed Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
title_sort Development and Validation of an ICP-MS/MS Method for the Multielemental Analysis of Cerebrospinal Fluid, Examination of Alzheimer's Disease Samples
dc.creator.none.fl_str_mv Pérez-Ramírez, R
Cuchillo-Ibáñez, I
Sánchez-Romero, R
Beltrán-Sanahuja, A
Escamilla, S
Molina-Gasset, R
Zetterberg, H
Blennow, K
Sáez-Valero, J
Todolí-Torro, J
author Pérez-Ramírez, R
author_facet Pérez-Ramírez, R
Cuchillo-Ibáñez, I
Sánchez-Romero, R
Beltrán-Sanahuja, A
Escamilla, S
Molina-Gasset, R
Zetterberg, H
Blennow, K
Sáez-Valero, J
Todolí-Torro, J
author_role author
author2 Cuchillo-Ibáñez, I
Sánchez-Romero, R
Beltrán-Sanahuja, A
Escamilla, S
Molina-Gasset, R
Zetterberg, H
Blennow, K
Sáez-Valero, J
Todolí-Torro, J
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Alzheimer's disease
biomarker
chemical elements
CSF
ICP-MS/MS
Mn
topic Alzheimer's disease
biomarker
chemical elements
CSF
ICP-MS/MS
Mn
description Multielemental analysis of cerebrospinal fluid (CSF) yields critical insights into the pathophysiology of neurological disorders and holds potential as a diagnostic and predictive tool for Alzheimer's disease (AD). The present work presents the development and validation of an inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) based method for multielemental determination in CSF, including metals and metalloids as analytes. As a proof of concept, the importance of the CSF element determination was evaluated in a cohort of patients with AD (n = 20) and non-AD controls (n = 19) who displayed typical levels of core CSF biomarkers (A beta 42, P-tau, and total-tau). Discrete sample introduction ICP-MS/MS procedure was effective for accurate and precise CSF analysis. The methodology provided better sensitivities and limits of detection than a conventional one based on sample dilution and analysis in continuous sample introduction mode, while only requiring a 20 mu L CSF sample volume. A total of 24 elements were encountered and quantified in CSF, with reduced levels of Mn, Cr, Se, Fe, and Zn in the CSF from AD patients and increased levels of Ag and Bi, compared with non-AD patients. Particularly, Mn fully discriminated AD from non-AD subjects, with binary regression analysis indicating that Mn was the most effective element to distinguish between AD and non-AD groups. Furthermore, distinctive correlation profiles were found between AD and non-AD controls for elements with AD core biomarkers and the alternative amyloidogenic sAPP beta fragment. Quantitative determination of metals, metalloids and non-metals displays differences associated with pathological status, serving as additional biomarkers for neurological diseases.
publishDate 2025
dc.date.none.fl_str_mv 2025
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fisabio.portalinvestigacion.com/publicaciones/20219
url https://fisabio.portalinvestigacion.com/publicaciones/20219
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Blackwell Publishing Inc.
publisher.none.fl_str_mv Blackwell Publishing Inc.
dc.source.none.fl_str_mv JOURNAL OF NEUROCHEMISTRY
ISSN: 14714159
ISSNe: 00223042
reponame:r-FISABIO. Repositorio Institucional de Producción Científica
instname:Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
instname_str Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO)
reponame_str r-FISABIO. Repositorio Institucional de Producción Científica
collection r-FISABIO. Repositorio Institucional de Producción Científica
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,811543

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