β-Amyloid in Cerebrospinal Fluid: How to Keep It Floating (Not Sticking) by Standardization of Preanalytic Processes and Collection Tubes

Abstract

Abstract Background Phosphorylated tau (pTau), total tau (tTau), and β-amyloid (Aβ) are established cerebrospinal fluid (CSF) biomarkers used to help diagnose Alzheimer disease. Preanalytic workups of CSF samples lack harmonization, making interlaboratory comparison of these biomarkers challenging. The Aβ adsorbs to sample tubes, yielding underestimated concentrations, and may result in false Alzheimer disease diagnosis. Our primary aim was to compare Aβ recovery across multiple polypropylene tubes and to test the stability of tTau, pTau, and Aβ in the best performing tube. Methods Eight polypropylene tubes were tested using 3 CSF pools with Aβ concentrations <500, 500–1000, and >1000 ng/L. All samples were analyzed in duplicate. Tubes were cut open to assess their different infrared adsorption spectra. Freshly drawn CSF from 14 patients was distributed into 4 Sarstedt 5-mL (no. 63.504.027; Sar5CSF) tubes, left at room temperature for up to 7 days, and analyzed for pTau, tTau, and Aβ by ELISA. Results Two Sarstedt 5-mL tubes and a Sarstedt 10-mL (Sar10CSF) tube showed significantly higher Aβ recovery at all 3 concentrations compared with the 5 other tubes. The infrared adsorption spectra of Sar10CSF and Sar5CSF tubes were practically identical, unlike the other tubes. No significant loss of pTau, tTau, and Aβ was observed in CSF left at room temperature for up to 7 days (P > 0.05). Conclusions Recovery of Aβ from Sar5CSF tubes is equivalent to Aβ recovery from Sar10CSF tubes. Levels of pTau, tTau, and Aβ were stable for at least 7 days at room temperature but not at 37 °C.