Importance of cerebrospinal fluid storage conditions for the Alzheimer’s disease diagnostics on an automated platform

Rosa Ferrer; Nuole Zhu; Javier Arranz; Inmaculada Porcel; Shaimaa El Bounasri; Oriol Sánchez; Soraya Torres; Josep Julve; Alberto Lleó; Francisco Blanco-Vaca; Daniel Alcolea; Mireia Tondo

doi:10.1515/cclm-2022-0134

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Importance of cerebrospinal fluid storage conditions for the Alzheimer’s disease diagnostics on an automated platform

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Veröffentlicht/Copyright: 12. April 2022

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Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 60 Heft 7

Abstract

Objectives

Alzheimer’s disease (AD) is considered the most common cause of dementia in older people. Cerebrospinal fluid (CSF) Aβ1-42, Aβ1-40, total Tau (t-Tau), and phospho Tau (p-Tau) are important biomarkers for the diagnosis, however, they are highly dependent on the pre-analytical conditions. Our aim was to investigate the potential influence of different storage conditions on the simultaneous quantification of these biomarkers in a fully-automated platform to accommodate easier pre-analytical conditions for laboratories.

Methods

CSF samples were obtained from 11 consecutive patients. Aβ1-42, Aβ1-40, p-Tau, and t-Tau were quantified using the LUMIPULSE G600II automated platform.

Results

Temperature and storage days significantly influenced Aβ1-42 and Aβ1-40 with concentrations decreasing with days spent at 4 °C. The use of the Aβ1-42/Aβ1-40 ratio could partly compensate it. P-Tau and t-Tau were not affected by any of the tested storage conditions. For conditions involving storage at 4 °C, a correction factor of 1.081 can be applied. Diagnostic agreement was almost perfect in all conditions.

Conclusions

Cutoffs calculated in samples stored at −80 °C can be safely used in samples stored at −20 °C for 15–16 days or up to two days at RT and subsequent freezing at −80 °C. For samples stored at 4 °C, cutoffs would require applying a correction factor, allowing to work with the certainty of reaching the same clinical diagnosis.

Keywords: Alzheimer’s disease; amyloid; automated platforms; biomarkers; cerebrospinal fluid; Tau

Corresponding authors: Daniel Alcolea, Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute (IIB) Sant Pau, C/Sant Quintí 89, 08041, Barcelona, Spain; and Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain; and Mireia Tondo, Department of Biochemistry, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute (IIB) Sant Pau, Barcelona, Spain; Center of Biomedical Investigation Network for Diabetes and Metabolic Diseases (CIBERDEM), Madrid, Spain; and Comisión de Neuroquímica y Enfermedades Neurológicas, Sociedad Española de Medicina de Laboratorio, Barcelona, Spain, Phone: +34 93 5537358, Fax: +34 93 553787, E-mail: mtondo@santpau.com

Funding source: CIBERDEM

Funding source: CIBERNED

Funding source: Instituto de Salud Carlos III

Award Identifier / Grant number: PI21/00140

Award Identifier / Grant number: PI18/00435

Award Identifier / Grant number: INT19/00016

Award Identifier / Grant number: PI17/01896

Award Identifier / Grant number: AC19/00103

Funding source: Fondo Europeo de Desarrollo Regional

Funding source: Unión Europea

Funding source: Generalitat de Catalunya

Award Identifier / Grant number: 2017-SGR-547

Award Identifier / Grant number: SLT006/17/125

Award Identifier / Grant number: SLT002/16/408

Funding source: Marató TV3

Award Identifier / Grant number: 20142610

Acknowledgments

We thank all the participants of this study and all the members of the clinical and biochemical teams involved in the study.

Research funding: This work was supported by CIBERDEM and CIBERNED and Instituto de Salud Carlos III (PI21/00140 to FB-V and MT, PI18/00435 and INT19/00016 to DA, PI17/01896 and AC19/00103 to AL), funded by Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, “Una manera de hacer Europa”. This work was also supported by Generalitat de Catalunya (2017-SGR-547, SLT006/17/125 to DA, SLT002/16/408 to AL) and “Marató TV3” foundation grants 20142610 to AL. We thank Fujirebio Europe NV for kindly providing the necessary reagents to perform the study.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: All participants gave written informed consent before enrollment in accordance with the guidelines of the local Ethics Committee.

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Received: 2022-02-15

Accepted: 2022-03-24

Published Online: 2022-04-12

Published in Print: 2022-06-27

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Artikel in diesem Heft

https://doi.org/10.1515/cclm-2022-0134

Schlagwörter für diesen Artikel

Alzheimer’s disease; amyloid; automated platforms; biomarkers; cerebrospinal fluid; Tau