Title
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Pre-analytical stability of novel cerebrospinal fluid biomarkers
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Author
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Abstract
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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 degrees C or room temperature (RT), or 1-4 months at - 20 degrees C; or up to 7 freeze/thaw (f/t) cycles, before final storage at - 80 degrees 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 degrees C ( - 27%), and with 6% after every f/t cycle. 5-Methyltetrahydrofolate (5MTHF) ( - 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. |
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Language
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English
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Source (journal)
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Clinica chimica acta. - Amsterdam, 1956, currens
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Publication
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Amsterdam
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2019
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ISSN
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0009-8981
[print]
1873-3492
[online]
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DOI
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10.1016/J.CCA.2019.07.024
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Volume/pages
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497
(2019)
, p. 204-211
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ISI
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000484878100031
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Pubmed ID
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31348908
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Full text (Publisher's DOI)
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Full text (open access)
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