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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; ... Zetterberg, H; + view all (2021) Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring , 13 (1) , Article e12168. 10.1002/dad2.12168. Green open access

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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 (P < .0001), and minor decreases in EDTA Aβ40 and EDTA p-tau181 were found after freeze-thaw cycle 4 (P < .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.

Type: Article
Title: Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration.
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/dad2.12168
Publisher version: https://doi.org/10.1002/dad2.12168
Language: English
Additional information: © 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Keywords: amyloid beta, biomarkers, blood, citrate, ethylenediaminetetraacetic acid, glial fibrillary acidic protein, lithium heparin, neurofilament light, phosphorylated tau, pre‐analytics, serum
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10130389
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