TY - JOUR
T1 - Pre-analytical stability of novel cerebrospinal fluid biomarkers
AU - Willemse, Eline A.J.
AU - Vermeiren, Yannick
AU - Garcia-Ayllon, Maria Salud
AU - Bridel, Claire
AU - De Deyn, Peter P.
AU - Engelborghs, Sebastiaan
AU - van der Flier, Wiesje M.
AU - Jansen, Erwin E.W.
AU - Lopez-Font, Inmaculada B.
AU - Mendes, Vera
AU - Manadas, Bruno
AU - de Roeck, Naomi
AU - Saez-Valero, Javier
AU - Struys, Eduard A.
AU - Vanmechelen, Eugeen
AU - Andreasson, Ulf
AU - Teunissen, Charlotte E.
N1 - Funding Information:
The authors thank Kees van Uffelen and Lev Yener for preparing part of the CSF stability sets used in this study. This research was financially supported by Biobanking and BioMolecular resources Research Infrastructure the Netherlands (BBMRI-NL), a research infrastructure financed by the Dutch Government (NWO 184.021.007) under project CP2013-68. This study commenced within the BIOMARKAPD program of the EU Joint Programme – Neurodegenerative Disease Research (JPND). Project supported by the European Regional Development Fund (ERDF) through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia, I.P. under the projects POCI-01-0145-FEDER-007440, POCI-01-0145-FEDER-016428, and POCI-01-0145-FEDER-016795, and by The National Mass Spectrometry Network (RNEM) under the contract POCI-01-0145-FEDER-402-022125. EV is co-founder of ADx NeuroSciences. SE received research funding from ADx Neurosciences (paid to institution). CT received non-financial support in the form of research consumables from ADx Neurosciences. EW, YV, MG, CB, PD, WF, EJ, IL, VM, BM, NR, JS, ES, and UA report no disclosures related to this project.
Funding Information:
The authors thank Kees van Uffelen and Lev Yener for preparing part of the CSF stability sets used in this study. This research was financially supported by Biobanking and BioMolecular resources Research Infrastructure the Netherlands (BBMRI-NL) , a research infrastructure financed by the Dutch Government ( NWO 184.021.007 ) under project CP2013-68. This study commenced within the BIOMARKAPD program of the EU Joint Programme – Neurodegenerative Disease Research (JPND) . Project supported by the European Regional Development Fund (ERDF) through the COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia , I.P., under the projects POCI-01-0145-FEDER-007440 , POCI-01-0145-FEDER-016428 , and POCI-01-0145-FEDER-016795 , and by The National Mass Spectrometry Network (RNEM) under the contract POCI-01-0145-FEDER-402-022125 .
Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/10
Y1 - 2019/10
N2 - Stability of the cerebrospinal fluid (CSF) composition under different pre-analytical conditions is relevant for the diagnostic potential of biomarkers. Our aim was to examine the pre-analytical stability of promising CSF biomarkers that are currently evaluated for their discriminative use in various neurological diseases. Pooled CSF was aliquoted and experimentally exposed to delayed storage: 0, 1, 2, 4, 24, 72, or 168 h at 4 °C or room temperature (RT), or 1–4 months at −20 °C; or up to 7 freeze/thaw (f/t) cycles, before final storage at −80 °C. Eleven CSF biomarkers were screened using immunoassays, liquid chromatography, or enzymatic methods. Levels of neurogranin (truncP75), chitinase-3-like protein (YKL-40), beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE) enzymatic activity, theobromine, secreted protein acidic and rich in cysteine-like 1 (SPARCL-1) and homovanillic acid (HVA) levels were not affected by the applied storage conditions. 3-Methoxy-4-hydroxyphenylglycol (MHPG) levels linearly and strongly decreased after 4 h at RT (−10%) or 24 h at 4 °C (−27%), and with 6% after every f/t cycle. 5-Methyltetrahydrofolate (5-MTHF) (−29% after 1 week at RT) and 5-hydroxyindoleacetic acid levels (5-HIAA) (−16% after 1 week at RT) were reduced and 3,4-dihydroxyphenylacetic acid (DOPAC) levels (+22% after 1 week at RT) increased, but only after >24 h at RT. Ten out of eleven potential CSF novel biomarkers showed very limited change under common storage and f/t conditions, suggesting that these CSF biomarkers can be trustfully tested under the pre-analytical conditions present across different cohorts.
AB - Stability of the cerebrospinal fluid (CSF) composition under different pre-analytical conditions is relevant for the diagnostic potential of biomarkers. Our aim was to examine the pre-analytical stability of promising CSF biomarkers that are currently evaluated for their discriminative use in various neurological diseases. Pooled CSF was aliquoted and experimentally exposed to delayed storage: 0, 1, 2, 4, 24, 72, or 168 h at 4 °C or room temperature (RT), or 1–4 months at −20 °C; or up to 7 freeze/thaw (f/t) cycles, before final storage at −80 °C. Eleven CSF biomarkers were screened using immunoassays, liquid chromatography, or enzymatic methods. Levels of neurogranin (truncP75), chitinase-3-like protein (YKL-40), beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), acetylcholinesterase (AChE) enzymatic activity, theobromine, secreted protein acidic and rich in cysteine-like 1 (SPARCL-1) and homovanillic acid (HVA) levels were not affected by the applied storage conditions. 3-Methoxy-4-hydroxyphenylglycol (MHPG) levels linearly and strongly decreased after 4 h at RT (−10%) or 24 h at 4 °C (−27%), and with 6% after every f/t cycle. 5-Methyltetrahydrofolate (5-MTHF) (−29% after 1 week at RT) and 5-hydroxyindoleacetic acid levels (5-HIAA) (−16% after 1 week at RT) were reduced and 3,4-dihydroxyphenylacetic acid (DOPAC) levels (+22% after 1 week at RT) increased, but only after >24 h at RT. Ten out of eleven potential CSF novel biomarkers showed very limited change under common storage and f/t conditions, suggesting that these CSF biomarkers can be trustfully tested under the pre-analytical conditions present across different cohorts.
KW - Assay validation
KW - Biomarkers
KW - Human cerebrospinal fluid
KW - Neurodegenerative diseases
KW - Pre-analytical stability
UR - https://www.scopus.com/pages/publications/85069842833
U2 - 10.1016/j.cca.2019.07.024
DO - 10.1016/j.cca.2019.07.024
M3 - Article
C2 - 31348908
AN - SCOPUS:85069842833
SN - 0009-8981
VL - 497
SP - 204
EP - 211
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
ER -