Okereke Olivia I, Xia Weiming, Irizarry Michael C, Sun Xiaoyan, Qiu Wei Q, Fagan Anne M, Mehta Pankaj D, Hyman Bradley T, Selkoe Dennis J, Grodstein Francine
Division of Aging, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
J Alzheimers Dis. 2009;16(2):277-85. doi: 10.3233/JAD-2009-0948.
Identifying biomarkers of Alzheimer's disease (AD) risk will be critical to effective AD prevention. Levels of circulating amyloid-beta (Abeta) 40 and 42 may be candidate biomarkers. However, properties of plasma Abeta assays must be established. Using five different protocols, blinded samples were used to assess: intra-assay reproducibility; impact of EDTA vs. heparin anticoagulant tubes; and effect of time-to-blood processing. In addition, percent recovery of known Abeta concentrations in spiked samples was assessed. Median intra-assay coefficients of variation for the assay protocols ranged from 6-24% for Abeta(40), and 8-14% for Abeta(42). There were no systematic differences in reproducibility by collection method. Plasma concentrations of Abeta (particularly Abeta(42) appeared stable in whole blood kept in ice packs and processed as long as 24 hours after collection. Recovery of expected concentrations was modest, ranging from -24% to 44% recovery of Abeta(40), and 17% to 61% of Abeta(42). In conclusion, across five protocols, plasma Abeta(40) and Abeta(42) levels were measured with generally low error, and measurements appeared similar in blood collected in EDTA versus heparin. While these preliminary findings suggest that measuring plasma Abeta(40) and Abeta(42) may be feasible in varied research settings, additional work in this area is necessary.
识别阿尔茨海默病(AD)风险的生物标志物对于有效的AD预防至关重要。循环淀粉样β蛋白(Aβ)40和42的水平可能是候选生物标志物。然而,必须确定血浆Aβ检测方法的特性。使用五种不同的方案,对盲法样本进行评估:检测内重复性;乙二胺四乙酸(EDTA)与肝素抗凝管的影响;以及血液处理时间的影响。此外,还评估了加标样本中已知Aβ浓度的回收率。检测方案的检测内变异系数中位数,Aβ40为6%-24%,Aβ42为8%-14%。采集方法在重复性方面没有系统差异。只要在采集后24小时内对保存在冰袋中的全血进行处理,Aβ(尤其是Aβ42)的血浆浓度似乎保持稳定。预期浓度的回收率适中,Aβ40的回收率为-24%至44%,Aβ42的回收率为17%至61%。总之,在五种方案中,血浆Aβ40和Aβ42水平的测量误差总体较低,并且在EDTA和肝素抗凝采集的血液中测量结果相似。虽然这些初步发现表明在不同的研究环境中测量血浆Aβ40和Aβ42可能是可行的,但该领域仍需要更多的研究工作。