@article{discovery10130389, month = {June}, volume = {13}, year = {2021}, title = {Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration.}, number = {1}, journal = {Alzheimer's \& Dementia: Diagnosis, Assessment \& Disease Monitoring}, note = {{\copyright} 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.}, 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 (A{\ensuremath{\beta}})42, A{\ensuremath{\beta}}40, 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�{\ensuremath{>}}�0.95) but gave significantly different absolute concentrations. Weaker correlations between tube types were found for A{\ensuremath{\beta}}42/40 (r�=�0.63-0.86) and serum t-tau (r�=�0.46-0.64). Freeze-thaw cycles highly influenced levels of serum A{\ensuremath{\beta}} and t-tau (P�{\ensuremath{<}}�.0001), and minor decreases in EDTA A{\ensuremath{\beta}}40 and EDTA p-tau181 were found after freeze-thaw cycle 4 (P�{\ensuremath{<}}�.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 A{\ensuremath{\beta}}42, A{\ensuremath{\beta}}40, and t-tau. Freeze-thaw cycles�{\ensuremath{>}}�3 should be avoided for p-tau181.}, author = {Ashton, NJ and Su{\'a}rez-Calvet, M and Karikari, TK and Lantero-Rodriguez, J and Snellman, A and Sauer, M and Simr{\'e}n, J and Minguillon, C and Fauria, K and Blennow, K and Zetterberg, H}, url = {https://doi.org/10.1002/dad2.12168}, keywords = {amyloid beta, biomarkers, blood, citrate, ethylenediaminetetraacetic acid, glial fibrillary acidic protein, lithium heparin, neurofilament light, phosphorylated tau, pre-analytics, serum} }