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 - Copyright © 2019 Elsevier B.V. All rights reserved.
PY - 2019/10/1
Y1 - 2019/10/1
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/inward/record.uri?partnerID=HzOxMe3b&scp=85069842833&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31348908
UR - http://www.scopus.com/inward/record.url?scp=85069842833&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.cca.2019.07.024
DO - https://doi.org/10.1016/j.cca.2019.07.024
M3 - Article
C2 - 31348908
SN - 0009-8981
VL - 497
SP - 204
EP - 211
JO - Clinica chimica acta; international journal of clinical chemistry
JF - Clinica chimica acta; international journal of clinical chemistry
ER -