Differences in Alzheimer's disease blood biomarker stability: Implications for the use of tau/amyloid ratios
Daniel J. Figdore, Bethany J. Schuder, Susan Ashrafzadeh‐Kian, Tina Gronquist, Joshua A. Bornhorst, Alicia Algeciras‐Schimnich
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.