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

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 (A...

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Autores: Ashton, Nicholas J., Suárez-Calvet, Marc, Karikari, Thomas K., Lantero Rodriguez, Juan, Snellman, Anniina, Sauer, Mathias, Simrén, Joel, Minguillón, Carolina, Fauria, Karine, Blennow, Kaj, Zetterberg, Henrik
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/49254
Acceso en línea:http://hdl.handle.net/10230/49254
http://dx.doi.org/10.1002/dad2.12168
Access Level:acceso abierto
Palabra clave:Amyloid beta
Biomarkers
Blood
Citrate
Ethylenediaminetetraacetic acid
Glial fibrillary acidic protein
Lithium heparin
Neurofilament light
Phosphorylated tau
Pre‐analytics
Serum
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oai_identifier_str oai:repositori.upf.edu:10230/49254
network_acronym_str ES
network_name_str España
repository_id_str
dc.title.none.fl_str_mv Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
title Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
spellingShingle Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
Ashton, Nicholas J.
Amyloid beta
Biomarkers
Blood
Citrate
Ethylenediaminetetraacetic acid
Glial fibrillary acidic protein
Lithium heparin
Neurofilament light
Phosphorylated tau
Pre‐analytics
Serum
title_short Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
title_full Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
title_fullStr Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
title_full_unstemmed Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
title_sort Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration
dc.creator.none.fl_str_mv Ashton, Nicholas J.
Suárez-Calvet, Marc
Karikari, Thomas K.
Lantero Rodriguez, Juan
Snellman, Anniina
Sauer, Mathias
Simrén, Joel
Minguillón, Carolina
Fauria, Karine
Blennow, Kaj
Zetterberg, Henrik
author Ashton, Nicholas J.
author_facet Ashton, Nicholas J.
Suárez-Calvet, Marc
Karikari, Thomas K.
Lantero Rodriguez, Juan
Snellman, Anniina
Sauer, Mathias
Simrén, Joel
Minguillón, Carolina
Fauria, Karine
Blennow, Kaj
Zetterberg, Henrik
author_role author
author2 Suárez-Calvet, Marc
Karikari, Thomas K.
Lantero Rodriguez, Juan
Snellman, Anniina
Sauer, Mathias
Simrén, Joel
Minguillón, Carolina
Fauria, Karine
Blennow, Kaj
Zetterberg, Henrik
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Amyloid beta
Biomarkers
Blood
Citrate
Ethylenediaminetetraacetic acid
Glial fibrillary acidic protein
Lithium heparin
Neurofilament light
Phosphorylated tau
Pre‐analytics
Serum
topic Amyloid beta
Biomarkers
Blood
Citrate
Ethylenediaminetetraacetic acid
Glial fibrillary acidic protein
Lithium heparin
Neurofilament light
Phosphorylated tau
Pre‐analytics
Serum
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/49254
http://dx.doi.org/10.1002/dad2.12168
url http://hdl.handle.net/10230/49254
http://dx.doi.org/10.1002/dad2.12168
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Alzheimers Dement (Amst). 2021;13(1):e12168
info:eu-repo/grantAgreement/EC/H2020/752310
info:eu-repo/grantAgreement/EC/H2020/860197
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869420546550136832
spelling Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegenerationAshton, Nicholas J.Suárez-Calvet, MarcKarikari, Thomas K.Lantero Rodriguez, JuanSnellman, AnniinaSauer, MathiasSimrén, JoelMinguillón, CarolinaFauria, KarineBlennow, KajZetterberg, HenrikAmyloid betaBiomarkersBloodCitrateEthylenediaminetetraacetic acidGlial fibrillary acidic proteinLithium heparinNeurofilament lightPhosphorylated tauPre‐analyticsSerumIntroduction: 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.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.Wiley202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/49254http://dx.doi.org/10.1002/dad2.12168reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésAlzheimers Dement (Amst). 2021;13(1):e12168info:eu-repo/grantAgreement/EC/H2020/752310info:eu-repo/grantAgreement/EC/H2020/860197© 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.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/492542026-06-12T07:21:37Z
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