An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels.

IF 7.6 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's Research & Therapy Pub Date : 2025-07-12 DOI:10.1186/s13195-025-01802-x

Ting Yang, Yi Ran Xu, Shanxue Jin, Nagendran Ramalingam, Jean-Pierre Bellier, Alexandra M Lish, Beth L Ostaszewski, Tracy Young-Pearse, Lei Liu, Hyun-Sik Yang, Jasmeer P Chhatwal, Trebor L Lawton, Dennis J Selkoe

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引用次数: 0

Abstract

Background: Diffusible Aβ oligomers (oAβ) confer cytotoxicity in Alzheimer's disease. The dynamic complexity of this hydrophobic analyte means few immunoassays exist to quantify oAβ in CSF and plasma.

Methods: We characterized antibody 71A1 to a cyclized dimer of Aβ9-18 for oAβ preference over monomers by surface plasmon resonance. We improved an earlier bead-based immunoassay by using 71A1 streptavidin plates for capture and N-terminal antibody 3D6 for detection. Numerous controls systematically validated accuracy.

Results: 71A1 showed highly selective binding kinetics to Aβ oligomers over monomers. It enriched bioactive oligomers from AD brain that altered neuronal excitatory currents and calcium transients. 71A1/3D6 immunoassay exhibited specificity and reproducibility in human biofluids. CSF oAβ levels correlated positively with CSF tau and phosphorylated-tau-181. APP and PS1 FAD mutations increased oAβ levels in human neuronal media.

Conclusions: CSF oAβ levels rise in concert with rising tau levels. A new plate-based ELISA offers improved consistency, less sample volume, and lower cost, thus better suited to quantify this challenging analyte.

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一种改进的免疫测定法检测人类生物体液中的Aβ低聚物：它们的脑脊液水平随着tau和磷tau水平的升高而升高。

背景：扩散性Aβ低聚物（oAβ）赋予阿尔茨海默病的细胞毒性。这种疏水分析物的动态复杂性意味着很少有免疫分析方法可以量化脑脊液和血浆中的oAβ。方法：采用表面等离子体共振方法对抗体71A1与a β9-18的环化二聚体进行了表征。我们改进了早期基于珠的免疫分析，使用71A1链亲和素板进行捕获，并使用n端抗体3D6进行检测。许多控制系统验证了准确性。结果：71A1表现出与Aβ低聚物的高度选择性结合动力学。它丰富了来自AD大脑的生物活性低聚物，改变了神经元兴奋电流和钙瞬态。71A1/3D6免疫分析法在人体液中具有特异性和可重复性。脑脊液oAβ水平与脑脊液tau和磷酸化tau-181呈正相关。APP和PS1 FAD突变增加了人神经介质中oAβ的水平。结论：脑脊液oAβ水平随tau水平升高而升高。一种新的基于板的ELISA提供了更好的一致性，更少的样本量和更低的成本，因此更适合于量化这种具有挑战性的分析物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Alzheimer's Research & Therapy 医学-神经病学

CiteScore

13.10

自引率

3.30%

发文量

172

审稿时长

>12 weeks

期刊介绍： Alzheimer's Research & Therapy is an international peer-reviewed journal that focuses on translational research into Alzheimer's disease and other neurodegenerative diseases. It publishes open-access basic research, clinical trials, drug discovery and development studies, and epidemiologic studies. The journal also includes reviews, viewpoints, commentaries, debates, and reports. All articles published in Alzheimer's Research & Therapy are included in several reputable databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, MEDLINE, PubMed, PubMed Central, Science Citation Index Expanded (Web of Science) and Scopus.