Differences in Alzheimer's disease blood biomarker stability: Implications for the use of tau/amyloid ratios

Abstract

INTRODUCTION

We compare the stability of phosphorylated tau (p-tau)217, amyloid beta (Aβ)42, Aβ40, Aβ42/40, and p-tau217/Aβ42 at different storage temperatures.

METHODS

Ten ethylenediaminetetraacetic acid–plasma sample aliquots stored at frozen, refrigerated, and ambient temperatures were tested at various timepoints up to 30 days. The mean percent change from baseline was calculated.

RESULTS

Aβ42 and Aβ40 concentrations decreased by >15% after 6 hours at ambient temperature and after 24 hours refrigerated, while p-tau217 remained stable over 72 hours with < 10% deviation from baseline at either storage temperature. The Aβ42/40 ratio remained relatively constant as each analyte concentration decreased concurrently, while the p-tau217/Aβ42 ratio deviated from baseline over time. All biomarkers were stable up to 30 days frozen.

DISCUSSION

Differences in the stability of Aβ42 and p-tau217 may lead to altered p-tau217/Aβ42 ratio results if samples are not handled properly during the pre-analytical testing phase. Ideally, samples should be frozen promptly and sent to the laboratory frozen.

Highlights

• Plasma phosphorylated tau (p-tau)217, amyloid beta (Aβ)42, Aβ40, Aβ42/40, and p-tau217/Aβ42 stability was assessed.
• P-tau217 was stable, but Aβ42 and Aβ40 started decreasing by 6 hours at ambient temperature.
• The analyte stability differences led to falsely increased p-tau217/Aβ42 ratios.
• Increases > 15% were seen in p-tau217/Aβ42 after 6 hours at ambient temperature or 24 hours at 4°C.