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- W2536956762 abstract "During different steps of cerebrospinal fluid (CSF) processing, pre-analytical variation factors could artificially influence proteins, resulting in changed biomarker levels not related to the patient biology. Pre-analytical variation, due to e.g. lot-to-lot variation, accounted for up to 25% of incorrect AD classifications based on the CSF profile (Vos et al., 2014, PlosOne). To avoid these confounding effects, we aimed to identify quality markers for CSF and, complementary, study the stability of CSF proteins under pre-analytical conditions in general. In the current study we aimed to detect changes in protein levels during specific pre-analytical conditions. We experimentally exposed CSF to extreme pre-analytical conditions: delayed processing at room temperature and 4°C for 1, 2, and 24 hours; delayed storage at room temperature and 4°C for 1 hour, 1 day, and 1 week; and 1, 4, and 8 freeze-and-thaw cycles. For each pre-analytical condition 3 pools were prepared. A reference sample per pool was kept at -80⁰C from the start. The CSF samples were measured with Somascan, to analyze the levels of 1129 proteins using aptamers. Effects of the treatments were statistically analyzed with ANOVA, corrected for pool number and for multiple testing (Bonferroni correction). We detected 8 markers with significantly changed levels after a delay of 24 hours between collection and centrifugation at room temperature. For the delay between centrifugation and storage, we found 8 different markers to be significantly changed after 1 week at room temperature. No changes in protein levels were observed during time delays at 4⁰C. None of the levels of 1129 markers were changed after up to 8 freeze-and-thaw cycles. Most proteins in CSF are stable upon extreme pre-analytical conditions. For both delayed processing and delayed storage 8 different markers were detected which were significantly altered in the most extreme condition. These markers need to be validated for their potential use as sentinel molecules for CSF quality. CSF seems insensitive for multiple freeze-and-thaw steps for a large number of proteins. Our results provide support for studying CSF with more confidence regarding the effects of potential pre-analytical confounders." @default.
- W2536956762 created "2016-10-28" @default.
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- W2536956762 date "2016-07-01" @default.
- W2536956762 modified "2023-09-28" @default.
- W2536956762 title "P1-201: Quality Indicators of Pre-Analytical Variation in Cerebrospinal Fluid Detected with Aptamer Screening" @default.
- W2536956762 doi "https://doi.org/10.1016/j.jalz.2016.06.949" @default.
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