Stability of blood-based biomarkers of Alzheimer's disease over multiple freeze-thaw cycles

Alzheimer's & Dementia Diagnosis, Assessment and Disease Monitoring
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Keshavan A, Helsegrave A, Zetterberg H and Schott JM.

Alzheimer's & Dementia Diagnosis, Assessment and Disease Monitoring

DOI: doi.org/10.1016/j.dadm.2018.06.001

Abstract

Introduction

Freeze-thaw instability may contribute to preanalytical variation in blood-based biomarker studies. We investigated the effects of up to four freeze-thaw cycles on single molecule array immunoassays of serum neurofilament light chain and plasma total tau, amyloid beta 1–40 (Aß40), and Aβ 1–42 (Aβ42).

Methods

Individuals who had peripheral venepuncture during investigation of suspected neurodegenerative disease were recruited. After standardized preprocessing, 200 μL of plasma and serum aliquots were stored at −80°C within 60 minutes. Aliquots underwent one to four freeze-thaw cycles.

Results

There was no significant difference across four freeze-thaw cycles for serum neurofilament light chain (n = 12), plasma total tau (n = 11), or plasma Aβ42 (n = 12). For plasma Aβ40 (n = 14), there were significant median reductions by ratios of .96 and .92 at the third and fourth cycles, respectively.

Discussion

Up to four freeze-thaw cycles do not influence single molecule array blood biomarkers of neurofilament light chain, total tau, or Aβ42, with at most minor reductions in Aβ40.