Yang Ting, Xu Yi Ran, Jin Shanxue, Ramalingam Nagendran, Bellier Jean-Pierre, Lish Alexandra M, Ostaszewski Beth L, Young-Pearse Tracy, Liu Lei, Yang Hyun-Sik, Chhatwal Jasmeer P, Lawton Trebor L, Selkoe Dennis J
Department of Neurology, Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, 60 Fenwood Road, Boston, MA, 02115, USA.
Center for Alzheimer Research and Treatment, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
Alzheimers Res Ther. 2025 Jul 12;17(1):153. doi: 10.1186/s13195-025-01802-x.
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.
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.
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.
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.
可扩散的Aβ寡聚体（oAβ）在阿尔茨海默病中具有细胞毒性。这种疏水性分析物的动态复杂性意味着用于定量脑脊液和血浆中oAβ的免疫测定方法很少。
我们通过表面等离子体共振表征了针对Aβ9 - 18环化二聚体的抗体71A1对oAβ相对于单体的偏好。我们通过使用71A1链霉亲和素板进行捕获和N端抗体3D6进行检测，改进了早期基于磁珠的免疫测定方法。大量对照系统地验证了准确性。
71A1对Aβ寡聚体显示出比对单体更高的选择性结合动力学。它从AD大脑中富集了改变神经元兴奋性电流和钙瞬变的生物活性寡聚体。71A1/3D6免疫测定在人体生物流体中表现出特异性和可重复性。脑脊液oAβ水平与脑脊液tau和磷酸化tau - 181呈正相关。APP和PS1家族性阿尔茨海默病（FAD）突变会增加人神经元培养基中的oAβ水平。
脑脊液oAβ水平与tau水平升高同步上升。一种新的基于平板的酶联免疫吸附测定（ELISA）提供了更高的一致性、更少的样本量和更低的成本，因此更适合定量这种具有挑战性的分析物。
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