Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration

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• dc.contributor.author Ashton, Nicholas J.
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Karikari, Thomas K.
• dc.contributor.author Lantero Rodriguez, Juan
• dc.contributor.author Snellman, Anniina
• dc.contributor.author Sauer, Mathias
• dc.contributor.author Simrén, Joel
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Fauria, Karine
• dc.contributor.author Blennow, Kaj
• dc.contributor.author Zetterberg, Henrik
• dc.date.accessioned 2021-12-20T08:02:58Z
• dc.date.available 2021-12-20T08:02:58Z
• dc.date.issued 2021
• dc.description.abstract Introduction: We tested how tube types (ethylenediaminetetraacetic acid [EDTA], serum, lithium heparin [LiHep], and citrate) and freeze-thaw cycles affect levels of blood biomarkers for Alzheimer's disease (AD) pathophysiology, glial activation, and neuronal injury. Methods: Amyloid beta (Aβ)42, Aβ40, phosphorylated tau181 (p-tau181), glial fibrillary acidic protein, total tau (t-tau), neurofilament light, and phosphorylated neurofilament heavy protein were measured using single molecule arrays. Results: LiHep demonstrated the highest mean value for all biomarkers. Tube types were highly correlated for most biomarkers (r > 0.95) but gave significantly different absolute concentrations. Weaker correlations between tube types were found for Aβ42/40 (r = 0.63-0.86) and serum t-tau (r = 0.46-0.64). Freeze-thaw cycles highly influenced levels of serum Aβ and t-tau (P < .0001), and minor decreases in EDTA Aβ40 and EDTA p-tau181 were found after freeze-thaw cycle 4 (P < .05). Discussion: The same tube type should be used in research studies on blood biomarkers. Individual concentration cut-offs are needed for each tube type in all tested biomarkers despite being highly correlated. Serum should be avoided for Aβ42, Aβ40, and t-tau. Freeze-thaw cycles > 3 should be avoided for p-tau181.
• dc.description.sponsorship MSC received funding from the European Union's Horizon 2020 Research and Innovation Program under the Marie Sklodowska-Curie action grant agreement No 752310, and currently receives funding from Instituto de Salud Carlos III (PI19/00155) and from the Spanish Ministry of Science, Innovation and Universities (Juan de la Cierva Programme grant IJC2018-037478-I). TKK holds a Brightfocus postdoctoral fellowship (#A2020812F), and was further supported by the Swedish Alzheimer Foundation (Alzheimerfonden), the Swedish Dementia Foundation (Demensförbundet), Parkinsonfonden, Gamla Tjänarinnor, the Aina (Ann) Wallströms and Mary-Ann Sjöbloms Foundation, the Gun and Bertil Stohnes foundation, and the Anna Lisa and Brother Björnsson's Foundation. AS was supported by the Paulo Foundation, and currently receives funding from the Orion Research Foundation sr. KB is supported by the Swedish Research Council (#2017-00915), the Alzheimer Drug Discovery Foundation (ADDF), USA (#RDAPB-201809-2016615), the Swedish Alzheimer Foundation (#AF-742881), Hjärnfonden, Sweden (#FO2017-0243), the Swedish state under the agreement between the Swedish government and the County Councils, the ALF-agreement (#ALFGBG-715986), the European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), and the National Institute of Health (NIH), USA, (grant #1R01AG068398-01). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2018-02532), the European Research Council (#681712), Swedish State Support for Clinical Research (#ALFGBG-720931), the Alzheimer Drug Discovery Foundation (ADDF), USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C and #ADSF-21-831377-C), the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2019-0228), the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 860197 (MIRIADE), and the UK Dementia Research Institute at UCL.
• dc.format.mimetype application/pdf
• dc.identifier.citation Ashton NJ, Suárez-Calvet M, Karikari TK, Lantero-Rodriguez J, Snellman A, Sauer M, Simrén J, Minguillon C, Fauria K, Blennow K, Zetterberg H. Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration. Alzheimers Dement (Amst). 2021;13(1):e12168. DOI: 10.1002/dad2.12168
• dc.identifier.doi http://dx.doi.org/10.1002/dad2.12168
• dc.identifier.issn 2352-8729
• dc.identifier.uri http://hdl.handle.net/10230/49254
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement (Amst). 2021;13(1):e12168
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/752310
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
• dc.rights © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
• dc.subject.keyword Amyloid beta
• dc.subject.keyword Biomarkers
• dc.subject.keyword Blood
• dc.subject.keyword Citrate
• dc.subject.keyword Ethylenediaminetetraacetic acid
• dc.subject.keyword Glial fibrillary acidic protein
• dc.subject.keyword Lithium heparin
• dc.subject.keyword Neurofilament light
• dc.subject.keyword Phosphorylated tau
• dc.subject.keyword Pre‐analytics
• dc.subject.keyword Serum
• dc.title Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion