Abstract
Objectives
Alzheimer’s disease (AD) is considered the most common cause of dementia in older people. Recently, blood-based markers (BBM) Aβ1-42, Aβ1-40, and phospho Tau181 (p-Tau181) have demonstrated the potential to transform the diagnosis and prognostic assessment of AD. Our aim was to investigate the effect of different storage conditions on the quantification of these BBM and to evaluate the interchangeability of plasma and serum samples.
Methods
Forty-two individuals with some degree of cognitive impairment were studied. Thirty further patients were retrospectively selected. Aβ1-42, Aβ1-40, and p-Tau181 were quantified using the LUMIPULSE-G600II automated platform. To assess interchangeability between conditions, correction factors for magnitudes that showed strong correlations were calculated, followed by classification consistency studies.
Results
Storing samples at 4 °C for 8–9 days was associated with a decrease in Aβ fractions but not when stored for 1–2 days. Using the ratio partially attenuated the pre-analytical effects. For p-Tau181, samples stored at 4 °C presented lower concentrations, whereas frozen samples presented higher ones. Concerning classification consistency in comparisons that revealed strong correlations (p-Tau181), the percentage of total agreement was greater than 90 % in a large number of the tested cut-offs values.
Conclusions
Our findings provide relevant information for the standardization of sample collection and storage in the analysis of AD BBM in an automated platform. This knowledge is crucial to ensure their introduction into clinical settings.
Funding source: Instituto de Salud Carlos III
Award Identifier / Grant number: PI21/00140; PI18/00435; INT19/00016; PI17/01896; A
Funding source: Horizon 2020 Framework Programme
Award Identifier / Grant number: H2020-SC1-BHC-2018-2020/GA 965422
Funding source: Generalitat de Catalunya
Award Identifier / Grant number: 2017-SGR-547; SLT006/17/125; SLT002/16/408
Funding source: Fundació la Marató de 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.
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Research funding: This work was supported by CIBERDEM and CIBERNED and Instituto de Salud Carlos III (PI21/00140 to 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), European Union’s Horizon 2020, ‘MES-CoBraD’ (H2020-SC1-BHC-2018-2020/GA 965422 to JF), and “Marató TV3” foundation grants 20142610 to AL. We thank Fujirebio Europe NV for kindly providing the necessary reagents to perform the study.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: All participants gave written informed consent before enrolment in accordance with the guidelines of the local Ethics Committee.
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