Despite the routine use of sandwich enzyme-linked immunosorbent assays (ELISAs) for quantifying tau levels in CSF and plasma, tau accumulations in the brains of patients with Alzheimer disease (AD) have rarely been evaluated by this method. Thus, by introducing several tau ELISAs that target different epitopes, we evaluated accumulated tau levels in postmortem brains depending on disease stage, brain areas, and other AD-related changes. Notably, tau levels in insoluble fraction determined by each ELISAs differ depending on the epitopes of antibodies: non-AD control samples yield relatively high signals when an antibody against the N-terminal region of tau is used. On the other hand, ELISAs combining antibodies against the later-middle to C-terminal regions of tau produced substantially increased signals from AD samples, compared to those from non-AD controls. Such ELISAs better distinguish AD and non-AD controls, and the results are more closely associated with Braak neurofibrillary tangles stage, Aβ accumulation, and glial markers. Moreover, these ELISAs can reflect the pattern of tau spread across brain regions. In conclusion, Tau ELISAs that combine antibodies against the later-middle to C-terminal regions of tau can better reflect neuropathological tau accumulation, which would enable to evaluate tau accumulation in the brain at a biochemical level.

中文翻译：

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阿尔茨海默病患者大脑中 Tau 蛋白积累的 ELISA 评估

尽管常规使用夹心酶联免疫吸附测定 (ELISA) 来量化 CSF 和血浆中的 tau 水平，但很少通过这种方法评估阿尔茨海默病 (AD) 患者大脑中的 tau 积累。因此，通过引入几种针对不同表位的 tau ELISA，我们评估了死后大脑中累积的 tau 水平，具体取决于疾病阶段、大脑区域和其他 AD 相关变化。值得注意的是，每种 ELISA 测定的不溶性部分中的 tau 水平因抗体的表位而异：当使用针对 tau 的 N 末端区域的抗体时，非 AD 对照样品会产生相对较高的信号。另一方面，结合针对 tau 的中后期至 C 末端区域的抗体的 ELISA 可从 AD 样本中产生显着增加的信号，与非 AD 对照组相比。此类 ELISA 更好地区分 AD 和非 AD 对照，结果与 Braak 神经原纤维缠结阶段、Aβ 积累和神经胶质标志物更密切相关。此外，这些 ELISA 可以反映 tau 跨大脑区域的分布模式。总之，结合针对 tau 中后期至 C 末端区域的抗体的 Tau ELISA 可以更好地反映神经病理学 tau 积累，这将能够在生化水平上评估大脑中的 tau 积累。