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Licensed Unlicensed Requires Authentication Published by De Gruyter April 12, 2022

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 EMAIL logo and Mireia Tondo ORCID logo EMAIL logo

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.


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:

Funding source: CIBERDEM

Funding source: CIBERNED

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.

  1. 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.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: Authors state no conflict of interest.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. 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

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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