Alzheimer's disease (AD) is the most common form of age-associated dementia. Several studies have predicted that AD is caused by the production and deposition of the β-amyloid peptide (Aβ) in the brain, which is one of pathologic hallmarks of AD. In particular, Aβ oligomers are reportedly the most toxic and pathogenic of other peptide forms. We previously developed Multimer Detection System-Oligomeric Amyloid-β (MDS-OAβ), a technique for measuring Aβ oligomerization in plasma to diagnose AD. Here, we clarified the molecular sizes of oligomers that can be detected by the MDS and investigated differences in plasma spiking with a synthetic Aβ peptide in the plasma of AD patients and individuals with non-AD neurological conditions. To determine Aβ oligomer sizes detectable by MDS, size exclusion chromatography (SEC) was first performed on incubated samples of synthetic Aβ42 peptides. As a result, no MDS signals were observed for the Aβ42 monomer fractions, but strong signals were found for oligomers of 7–35-mers long. Also, an amplified luminescent proximity homogeneous assay-linked immunoassay (AlphaLISA) was used to confirm that synthetic Aβ peptides not only recruited endogenous Aβ in plasma but also induced significantly stronger seeding in AD plasma than in healthy control plasma. In addition, the absence of the MDS signals in Aβ-depleted plasma confirmed that the increased oligomerization tendency in AD plasma is dependent on the presence of endogenous Aβ in plasma. Therefore, the MDS-OAβ measurement of oligomerization differences in plasma after incubation with spiked synthetic Aβ peptides has significant potential in AD diagnosis.

阿尔茨海默病 (AD) 是最常见的与年龄相关的痴呆症。多项研究预测，AD是由大脑中β-淀粉样肽（Aβ）的产生和沉积引起的，这是AD的病理标志之一。特别是，据报道，Aβ 寡聚体是其他肽形式中毒性和致病性最强的。我们之前开发了多聚体检测系统-寡聚淀粉样蛋白-β (MDS-OAβ)，这是一种测量血浆中 Aβ 寡聚化以诊断 AD 的技术。在这里，我们阐明了 MDS 可以检测到的低聚物的分子大小，并研究了 AD 患者和非 AD 神经系统疾病个体血浆中合成 Aβ 肽在血浆中的差异。为了确定 MDS 可检测的 Aβ 寡聚体大小，首先对合成 Aβ42 肽的孵育样品进行尺寸排阻色谱 (SEC)。结果，没有观察到 Aβ42 单体级分的 MDS 信号，但发现了 7-35 聚体长的低聚物的强信号。此外，使用放大的发光邻近均相测定相关免疫测定 (AlphaLISA) 来确认合成 Aβ 肽不仅在血浆中募集内源性 Aβ，而且在 AD 血浆中比在健康对照血浆中诱导显着更强的接种。此外，Aβ 耗尽血浆中 MDS 信号的缺失证实 AD 血浆中寡聚化趋势的增加取决于血浆中内源性 Aβ 的存在。所以，