Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers
Autor(a) principal: | |
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Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/109154 https://doi.org/10.3389/fneur.2015.00153 |
Resumo: | Introduction: Core cerebrospinal fluid (CSF) biomarkers – Aβ42, Tau, and phosphorylated Tau (pTau) – have been recently incorporated in the revised criteria for Alzheimer’s disease (AD). However, their widespread clinical application lacks standardization. Preanalytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. Aim: In this study, we aim to surpass the efforts from previous studies, by employing a multicenter approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Methods: Four different centers participated in this study and followed the same established protocol. CSF samples were analyzed for three biomarkers (Aβ42, Tau, and pTau) and tested for different spinning conditions [temperature: room temperature (RT) vs. 4°C; speed: 500 vs. 2000 vs. 3000 g], storage volume variations (25, 50, and 75% of tube total volume), as well as freezing-thaw cycles (up to five cycles). The influence of sample routine parameters, inter-center variability, and relative value of each biomarker (reported as normal/abnormal) was analyzed. Results: Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non-centrifugation or centrifugation at RT, compared to 4°C, led to higher Aβ42 levels. Reducing CSF storage volume from 75 to 50% of total tube capacity decreased Aβ42 concentration (within analytical CV of the assay), whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to five freeze–thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than three times. Conclusion:This systematic study reinforces the need for CSF centrifugation at 4°C prior to storage and highlights the influence of storage conditions in Aβ42 levels.This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-labvariability of CSF-AD biomarkers evaluation. |
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Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD BiomarkersAlzheimer’s disease; BIOMARKAPD; biomarkers; cerebrospinal fluid; phosphorylated tau protein; standardized operating procedures; tau protein; β-amyloidIntroduction: Core cerebrospinal fluid (CSF) biomarkers – Aβ42, Tau, and phosphorylated Tau (pTau) – have been recently incorporated in the revised criteria for Alzheimer’s disease (AD). However, their widespread clinical application lacks standardization. Preanalytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. Aim: In this study, we aim to surpass the efforts from previous studies, by employing a multicenter approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Methods: Four different centers participated in this study and followed the same established protocol. CSF samples were analyzed for three biomarkers (Aβ42, Tau, and pTau) and tested for different spinning conditions [temperature: room temperature (RT) vs. 4°C; speed: 500 vs. 2000 vs. 3000 g], storage volume variations (25, 50, and 75% of tube total volume), as well as freezing-thaw cycles (up to five cycles). The influence of sample routine parameters, inter-center variability, and relative value of each biomarker (reported as normal/abnormal) was analyzed. Results: Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non-centrifugation or centrifugation at RT, compared to 4°C, led to higher Aβ42 levels. Reducing CSF storage volume from 75 to 50% of total tube capacity decreased Aβ42 concentration (within analytical CV of the assay), whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to five freeze–thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than three times. Conclusion:This systematic study reinforces the need for CSF centrifugation at 4°C prior to storage and highlights the influence of storage conditions in Aβ42 levels.This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-labvariability of CSF-AD biomarkers evaluation.Frontiers Media S.A.2015info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109154http://hdl.handle.net/10316/109154https://doi.org/10.3389/fneur.2015.00153eng1664-2295Leitão, Maria JoãoBaldeiras, InêsHerukka, Sanna-KaisaPikkarainen, MariaLeinonen, VilleSimonsen, Anja HviidPerret-Liaudet, ArmandFourier, AnthonyQuadrio, IsabelleVeiga, Pedro MotaOliveira, Catarina Resende deinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-09-29T08:52:07Zoai:estudogeral.uc.pt:10316/109154Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:21.127624Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
title |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
spellingShingle |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers Leitão, Maria João Alzheimer’s disease; BIOMARKAPD; biomarkers; cerebrospinal fluid; phosphorylated tau protein; standardized operating procedures; tau protein; β-amyloid |
title_short |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
title_full |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
title_fullStr |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
title_full_unstemmed |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
title_sort |
Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers |
author |
Leitão, Maria João |
author_facet |
Leitão, Maria João Baldeiras, Inês Herukka, Sanna-Kaisa Pikkarainen, Maria Leinonen, Ville Simonsen, Anja Hviid Perret-Liaudet, Armand Fourier, Anthony Quadrio, Isabelle Veiga, Pedro Mota Oliveira, Catarina Resende de |
author_role |
author |
author2 |
Baldeiras, Inês Herukka, Sanna-Kaisa Pikkarainen, Maria Leinonen, Ville Simonsen, Anja Hviid Perret-Liaudet, Armand Fourier, Anthony Quadrio, Isabelle Veiga, Pedro Mota Oliveira, Catarina Resende de |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Leitão, Maria João Baldeiras, Inês Herukka, Sanna-Kaisa Pikkarainen, Maria Leinonen, Ville Simonsen, Anja Hviid Perret-Liaudet, Armand Fourier, Anthony Quadrio, Isabelle Veiga, Pedro Mota Oliveira, Catarina Resende de |
dc.subject.por.fl_str_mv |
Alzheimer’s disease; BIOMARKAPD; biomarkers; cerebrospinal fluid; phosphorylated tau protein; standardized operating procedures; tau protein; β-amyloid |
topic |
Alzheimer’s disease; BIOMARKAPD; biomarkers; cerebrospinal fluid; phosphorylated tau protein; standardized operating procedures; tau protein; β-amyloid |
description |
Introduction: Core cerebrospinal fluid (CSF) biomarkers – Aβ42, Tau, and phosphorylated Tau (pTau) – have been recently incorporated in the revised criteria for Alzheimer’s disease (AD). However, their widespread clinical application lacks standardization. Preanalytical sample handling and storage play an important role in the reliable measurement of these biomarkers across laboratories. Aim: In this study, we aim to surpass the efforts from previous studies, by employing a multicenter approach to assess the impact of less studied CSF pre-analytical confounders in AD-biomarkers quantification. Methods: Four different centers participated in this study and followed the same established protocol. CSF samples were analyzed for three biomarkers (Aβ42, Tau, and pTau) and tested for different spinning conditions [temperature: room temperature (RT) vs. 4°C; speed: 500 vs. 2000 vs. 3000 g], storage volume variations (25, 50, and 75% of tube total volume), as well as freezing-thaw cycles (up to five cycles). The influence of sample routine parameters, inter-center variability, and relative value of each biomarker (reported as normal/abnormal) was analyzed. Results: Centrifugation conditions did not influence biomarkers levels, except for samples with a high CSF total protein content, where either non-centrifugation or centrifugation at RT, compared to 4°C, led to higher Aβ42 levels. Reducing CSF storage volume from 75 to 50% of total tube capacity decreased Aβ42 concentration (within analytical CV of the assay), whereas no change in Tau or pTau was observed. Moreover, the concentration of Tau and pTau appears to be stable up to five freeze–thaw cycles, whereas Aβ42 levels decrease if CSF is freeze-thawed more than three times. Conclusion:This systematic study reinforces the need for CSF centrifugation at 4°C prior to storage and highlights the influence of storage conditions in Aβ42 levels.This study contributes to the establishment of harmonized standard operating procedures that will help reducing inter-labvariability of CSF-AD biomarkers evaluation. |
publishDate |
2015 |
dc.date.none.fl_str_mv |
2015 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/109154 http://hdl.handle.net/10316/109154 https://doi.org/10.3389/fneur.2015.00153 |
url |
http://hdl.handle.net/10316/109154 https://doi.org/10.3389/fneur.2015.00153 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1664-2295 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Frontiers Media S.A. |
publisher.none.fl_str_mv |
Frontiers Media S.A. |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799134136441503744 |