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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Detalles Bibliográficos
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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2025
País:España
Institución: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
Acceso en línea:https://fisabio.portalinvestigacion.com/publicaciones/20219
Access Level:acceso abierto
Palabra clave:Alzheimer's disease
biomarker
chemical elements
CSF
ICP-MS/MS
Mn
Descripción
Sumario: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.