Department of Psychiatry and Psychotherapy, University Medical Center Goettingen (UMG), Georg-August-University, Von-Siebold-Str. 5, D-37075, Goettingen, Germany.
German Center for Neurodegenerative Diseases (DZNE), Von-Siebold-Str. 3a, D-37075, Goettingen, Germany.
Alzheimers Res Ther. 2018 Dec 8;10(1):121. doi: 10.1186/s13195-018-0448-x.
The quantification of amyloid-beta (Aβ) peptides in blood plasma as potential biomarkers of Alzheimer's disease (AD) is hampered by very low Aβ concentrations and the presence of matrix components that may interfere with the measurements.
We developed a two-step immunoassay for the simultaneous measurement of the relative levels of Aβ38, Aβ40 and Aβ42 in human EDTA plasma. The assay was employed for the study of 23 patients with dementia of the Alzheimer's type (AD-D) and 17 patients with dementia due to other reasons (OD). We examined relationships with the clinical diagnosis, cerebral Aβ load as quantified by amyloid-positron emission tomography, apolipoprotein E genotype, Aβ levels and Tau protein in cerebrospinal fluid.
Preconcentration of plasma Aβ peptides by immunoprecipitation substantially facilitated their immunological measurements. The Aβ42/Aβ40 and Aβ42/Aβ38 ratios were statistically significantly lower in the AD-D patients than in the OD group. The areas under the receiver operating characteristic curves reached 0.87 for the Aβ42/Aβ40 ratio and 0.80 for the Aβ42/Aβ38 ratio.
The measurement of plasma Aβ peptides with an immunological assay can be improved by preconcentration via immunoprecipitation with an antibody against the Aβ amino-terminus and elution of the captured peptides by heating in a mild detergent-containing buffer. Our findings support the Aβ42/Aβ40 ratio in blood plasma as a promising AD biomarker candidate which correlates significantly with the validated core biomarkers of AD. Further studies will be needed for technical advancement of the assay and validation of the biomarker findings.
由于血液中淀粉样蛋白-β（Aβ）肽的浓度非常低，并且存在可能干扰测量的基质成分，因此将其量化作为阿尔茨海默病（AD）的潜在生物标志物受到阻碍。
我们开发了一种两步免疫测定法，用于同时测量人 EDTA 血浆中 Aβ38、Aβ40 和 Aβ42 的相对水平。该测定法用于研究 23 例阿尔茨海默病痴呆（AD-D）患者和 17 例其他原因痴呆（OD）患者。我们检查了与临床诊断、脑 Aβ 负荷（通过淀粉样蛋白正电子发射断层扫描定量）、载脂蛋白 E 基因型、Aβ 水平和脑脊液 Tau 蛋白的关系。
通过免疫沉淀对血浆 Aβ 肽进行预浓缩，大大促进了它们的免疫学测量。AD-D 患者的 Aβ42/Aβ40 和 Aβ42/Aβ38 比值明显低于 OD 组。Aβ42/Aβ40 比值和 Aβ42/Aβ38 比值的受试者工作特征曲线下面积分别达到 0.87 和 0.80。
通过用针对 Aβ 氨基末端的抗体进行免疫沉淀预浓缩，并用含温和洗涤剂的缓冲液加热洗脱捕获的肽，可以改善免疫测定法测量血浆 Aβ 肽的方法。我们的发现支持血液 Aβ42/Aβ40 比值作为有前途的 AD 生物标志物候选物，与 AD 的经过验证的核心生物标志物显著相关。需要进一步的研究来推进该测定法的技术进步并验证生物标志物的发现。
