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Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration

Ashton NJ, Suárez-Calvet M, Karikari TK, Lantero-Rodriguez J, Snellman A, Sauer M, Simrén J, Minguillon C, Fauria K, Blennow K, Zetterberg H.

Abstract

Introduction: We tested how tube types (ethylenediaminetetraacetic acid [EDTA], serum, lithium heparin [LiHep], and citrate) and freeze-thaw cycles affect levels of blood biomarkers for Alzheimer's disease (AD) pathophysiology, glial activation, and neuronal injury.

Methods: Amyloid beta (Aβ)42, Aβ40, phosphorylated tau181 (p-tau181), glial fibrillary acidic protein, total tau (t-tau), neurofilament light, and phosphorylated neurofilament heavy protein were measured using single molecule arrays.

Results: LiHep demonstrated the highest mean value for all biomarkers. Tube types were highly correlated for most biomarkers (r > 0.95) but gave significantly different absolute concentrations. Weaker correlations between tube types were found for Aβ42/40 (r = 0.63-0.86) and serum t-tau (r = 0.46-0.64). Freeze-thaw cycles highly influenced levels of serum Aβ and t-tau (< .0001), and minor decreases in EDTA Aβ40 and EDTA p-tau181 were found after freeze-thaw cycle 4 (< .05).

Discussion: The same tube type should be used in research studies on blood biomarkers. Individual concentration cut-offs are needed for each tube type in all tested biomarkers despite being highly correlated. Serum should be avoided for Aβ42, Aβ40, and t-tau. Freeze-thaw cycles > 3 should be avoided for p-tau181.

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Reference

Ashton NJ, Suárez-Calvet M, Karikari TK, Lantero-Rodriguez J, Snellman A, Sauer M, Simrén J, Minguillon C, Fauria K, Blennow K, Zetterberg H. Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration. Alzheimers Dement (Amst). 2021 Jun 2;13(1):e12168. doi: 10.1002/dad2.12168. PMID: 34124336; PMCID: PMC8171159.