Willemse Eline A J, van Uffelen Kees W J, van der Flier Wiesje M, Teunissen Charlotte E
Department of Neurology, Neurochemistry Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
Department of Neurology, Alzheimer Center, Amsterdam Neuroscience, VU University Medical Center, Amsterdam, The Netherlands.
Alzheimers Dement (Amst). 2017 Apr 4;8:45-50. doi: 10.1016/j.dadm.2017.03.005. eCollection 2017.
We studied the effect of long-term storage at -80°C on cerebrospinal fluid (CSF) biomarker levels. Our approach assumed consistency of mean biomarker levels in a homogenous Alzheimer's disease patient cohort over time.
We selected 148 Alzheimer's disease samples that had inclusion dates equally distributed over the years 2001 to 2013 from our biobank. The concentrations of CSF biomarkers, amyloid β (Aβ), total tau (T-tau), and phosphorylated tau (P-tau), were measured with one enzyme-linked immunosorbent assay lot. Results were compared with historical results obtained at biobank inclusion.
Linear regression analyses showed that the levels of CSF biomarkers, Aβ, T-tau, and P-tau, were not related to storage time at -80°C (β = 0.015, 0.048, and 0.0016 pg/mL per day, not significant). However, the differences between remeasured concentrations of Aβ and concentrations at biobank inclusion measured for more than 30 assay batches increased with increasing time difference.
The levels of CSF biomarkers, Aβ, T-tau, and P-tau, did not significantly change during the maximum period of 12 years of storage at -80°C. Batch variation for Aβ is a factor that should be controlled for when using historical cohorts.
我们研究了在 -80°C 长期储存对脑脊液(CSF)生物标志物水平的影响。我们的方法假定在一个同质的阿尔茨海默病患者队列中,平均生物标志物水平随时间保持一致。
我们从生物样本库中选取了148份阿尔茨海默病样本,这些样本的纳入日期在2001年至2013年期间均匀分布。使用一批酶联免疫吸附测定法测量脑脊液生物标志物淀粉样β蛋白(Aβ)、总tau蛋白(T-tau)和磷酸化tau蛋白(P-tau)的浓度。将结果与生物样本库纳入时获得的历史结果进行比较。
线性回归分析表明,脑脊液生物标志物Aβ、T-tau和P-tau的水平与在 -80°C 下的储存时间无关(β = 每天0.015、0.048和0.0016 pg/mL,无显著性差异)。然而,对于超过30个检测批次,重新测量的Aβ浓度与生物样本库纳入时的浓度之间的差异随着时间差的增加而增大。
在 -80°C 下最长12年的储存期内,脑脊液生物标志物Aβ、T-tau和P-tau的水平没有显著变化。在使用历史队列时,Aβ的批次差异是一个需要控制的因素。