ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease
ELISA Evaluation of Tau Accumulation in the Brains of Patients with Alzheimer Disease
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ELISA 评估阿尔茨海默病患者大脑中 Tau 蛋白的积累
DOI：
10.1093/jnen/nlab047
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Sato Naoyuki
中科院分区：
文献类型：
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作者：
Shinohara Mitsuru;Hirokawa Junko;Shimodaira Akemi;Tashiro Yoshitaka;Suzuki Kaoru;Gheni Ghupurjan;Fukumori Akio;Matsubara Tomoyasu;Morishima Maho;Saito Yuko;Murayama Shigeo;Sato Naoyuki
尽管常规使用夹心酶联免疫吸附测定（ELISA）来定量CSF和血浆中的tau水平，但阿尔茨海默病（AD）患者脑中的tau积累很少通过该方法进行评估。因此，通过引入几种靶向不同表位的tau ELISA，我们根据疾病阶段、脑区和其他AD相关变化评估了死后脑中累积的tau水平。值得注意的是，通过每种ELISA测定的不溶性级分中的tau水平根据抗体的表位而不同：当使用针对tau的N末端区域的抗体时，非AD对照样品产生相对高的信号。另一方面，与来自非AD对照的那些相比，组合针对tau的后中部至C末端区域的抗体的ELISA产生了来自AD样品的显著增加的信号。这种ELISA可以更好地区分AD和非AD对照，并且结果与Braak神经元缠结分期、Aβ积聚和胶质标志物更密切相关。此外，这些ELISA可以反映tau在大脑区域中的分布模式。总之，结合针对tau的后中部至C末端区域的联合收割机抗体的Tau ELISA可以更好地反映神经病理学tau积累，这将使得能够在生物化学水平上评估脑中的tau积累。
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.