en
Scientific article
English

Pre-analytical stability of novel cerebrospinal fluid biomarkers

Published inClinica chimica acta, vol. 497, p. 204-211
Publication date2019-10
First online date2019-07-23
Abstract

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.

eng
Keywords
  • Assay validation
  • Biomarkers
  • Human cerebrospinal fluid
  • Neurodegenerative diseases
  • Pre-analytical stability
  • Biomarkers / cerebrospinal fluid
  • Biomarkers / chemistry
  • Biomarkers / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / metabolism
Affiliation Not a UNIGE publication
Citation (ISO format)
WILLEMSE, Eline A J et al. Pre-analytical stability of novel cerebrospinal fluid biomarkers. In: Clinica chimica acta, 2019, vol. 497, p. 204–211. doi: 10.1016/j.cca.2019.07.024
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Article (Published version)
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ISSN of the journal1873-3492
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Creation12/22/2022 1:54:00 PM
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