# Evaluation of preanalytical factors on quantification of amyloid-β (1-42), phosphorylated tau 181, and total tau in cerebrospinal fluid

## TL;DR

This study examines how refrigerated transportation and hemolysis affect Alzheimer's disease biomarker measurements in cerebrospinal fluid.

## Contribution

The study reveals that hemolysis significantly impacts Aβ42 measurements but not other biomarkers, while refrigeration has minimal effect.

## Key findings

- Refrigerated transportation for 14 days had less than 10% effect on biomarker concentrations.
- Hemolysis caused a more than 10% decrease in Aβ42 measurements.
- Phosphorylated tau 181 and total tau were not affected by hemolysis.

## Abstract

Cerebrospinal fluid (CSF) biomarkers for Alzheimer disease are US Food and Drug Administration approved and implemented on automated platforms, allowing for widespread use and higher throughput. Although low-bind polypropylene tubes for accurate quantification of amyloid-β (Aβ) have been well studied, less is known about the impact of other common preanalytical variables on quantification of biomarkers for Alzheimer disease. This study evaluated the effects of refrigerated transportation and hemolysis on the concentrations of Aβ42, phosphorylated tau 181, and total tau.

The Roche Diagnostics Elecsys β-Amyloid (1-42) CSF II, Elecsys Phospho-Tau (181P) CSF, and Elecsys Total-Tau CSF assays were used on the Roche cobas pro e 801 platform to measure protein concentrations in residual CSF samples. Paired-difference testing was performed to determine the effects of simulated transportation and hemolysis on each analyte.

For all 3 analytes, less than 10% difference was observed between the concentrations measured on day 0 and after 14 days of transportation and refrigeration. In contrast, 2.26 g/L free hemoglobin resulted in more than 10% negative bias in Aβ42 measurement compared with the 0 g/L control but did not affect phosphorylated tau 181 or total tau concentrations.

Refrigerated transportation did not affect the analysis of Aβ42, phosphorylated tau 181, or total tau, whereas hemolysis can negatively affect results of Aβ42.