分析前程序对阿尔茨海默病病理生理学、神经胶质细胞激活和神经退行性变血液生物标志物的影响。
Effects of pre-analytical procedures on blood biomarkers for Alzheimer's pathophysiology, glial activation, and neurodegeneration.
作者信息
Ashton Nicholas J, Suárez-Calvet Marc, Karikari Thomas K, Lantero-Rodriguez Juan, Snellman Anniina, Sauer Mathias, Simrén Joel, Minguillon Carolina, Fauria Karine, Blennow Kaj, Zetterberg Henrik
机构信息
Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology The Sahlgrenska Academy University of Gothenburg Gothenburg Sweden.
Wallenberg Centre for Molecular and Translational Medicine Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg Gothenburg Sweden.
出版信息
Alzheimers Dement (Amst). 2021 Jun 2;13(1):e12168. doi: 10.1002/dad2.12168. eCollection 2021.
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.
引言
我们测试了试管类型（乙二胺四乙酸[EDTA]、血清、锂肝素[LiHep]和柠檬酸盐）以及冻融循环如何影响阿尔茨海默病（AD）病理生理学、神经胶质细胞激活和神经元损伤的血液生物标志物水平。
方法
使用单分子阵列测量淀粉样β蛋白（Aβ）42、Aβ40、磷酸化tau181（p-tau181）、神经胶质纤维酸性蛋白、总tau蛋白（t-tau）、神经丝轻链和磷酸化神经丝重链蛋白。
结果
LiHep对所有生物标志物的均值最高。大多数生物标志物的试管类型之间高度相关（r>0.95），但绝对浓度差异显著。Aβ42/40（r=0.63-0.86）和血清t-tau（r=0.46-0.64）的试管类型之间相关性较弱。冻融循环对血清Aβ和t-tau水平有高度影响（<.0001），在第4次冻融循环后发现EDTA Aβ40和EDTA p-tau181略有下降（<.05）。
讨论
在血液生物标志物的研究中应使用相同的试管类型。尽管所有测试生物标志物的试管类型高度相关，但每种试管类型都需要单独的浓度临界值。对于Aβ42、Aβ40和t-tau应避免使用血清。对于p-tau181应避免超过3次的冻融循环。
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