Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/109154
Title: Chasing the Effects of Pre-Analytical Confounders - A Multicenter Study on CSF-AD Biomarkers
Authors: 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 
Keywords: Alzheimer’s disease; BIOMARKAPD; biomarkers; cerebrospinal fluid; phosphorylated tau protein; standardized operating procedures; tau protein; β-amyloid
Issue Date: 2015
Publisher: Frontiers Media S.A.
Project: ThisstudywasdoneunderthescopeofanEUJointProgramme– NeurodegenerativeDiseaseResearch(JPND)–BIOMARKAPD project.Theprojectissupportedthroughthefollowingfund- ingorganizationsundertheaegisofJPND– www.jpnd.eu: The PortugueseScienceFoundation(FCT-JPND/0005/2011project), Portugal;InnovationFundDenmarkgrantnumber:0603-00470B; AcademyofFinland,ResearchCouncilforHealth,decisionn 263193; ANRgrantnumber:12-JPND-001-16. 
metadata.degois.publication.title: Frontiers in Neurology
metadata.degois.publication.volume: 6
metadata.degois.publication.issue: JUL
Abstract: 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.
URI: https://hdl.handle.net/10316/109154
ISSN: 1664-2295
DOI: 10.3389/fneur.2015.00153
Rights: openAccess
Appears in Collections:FMUC Medicina - Artigos em Revistas Internacionais
I&D CNC - Artigos em Revistas Internacionais

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