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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



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.


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.


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.


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


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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