Uncovering elevated tau TPP motif phosphorylation in the brain of Alzheimer's disease patients.
Uncovering elevated tau TPP motif phosphorylation in the brain of Alzheimer's disease patients.
复制标题
揭示阿尔茨海默病患者大脑中 tau TPP 基序磷酸化水平升高。
DOI：
10.1002/alz.13557
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发表时间：
2024
期刊：
影响因子：
--
通讯作者：
Liu,Lei
中科院分区：
文献类型：
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作者：
Bellier,Jean-Pierre;Cai,Yuqi;Alam,SarahM;Wiederhold,Thorsten;Aiello,Arica;Vogelgsang,JonathanS;Berretta,Sabina;Chhatwal,JasmeerP;Selkoe,DennisJ;Liu,Lei
引言在阿尔茨海默病（AD）中发生tau蛋白的大量翻译后修饰，并且它们对发病机制和生物标志物的开发至关重要。几个有希望的tau标记物，pT 181，pT 217和pT 231，依赖于共同的分子基序苏氨酸-脯氨酸-脯氨酸（TPP）内增加的磷酸化。然后联合免疫组化（IHC）和免疫测定（ELISA）为了广泛地检测AD脑中tau TPP基序的磷酸化，通过IHC和ELISA检测的tau负荷与所有TPP位点的Braak阶段相关。此外，我们观察到区域的变异性，在多个大脑中的四个TPP基序磷酸化位点的散发性AD patients. PromissionWe的结论是，有一个升高的TPP tau磷酸化在AD脑疾病的进展。pTPP tau的区域变异性表明，检查不同的磷酸化位点对于全面评估tau病理学至关重要。
INTRODUCTIONA wide array of post‐translational modifications of the tau protein occurs in Alzheimer's disease (AD) and they are critical to pathogenesis and biomarker development. Several promising tau markers, pT181, pT217, and pT231, rely on increased phosphorylation within a common molecular motif threonine‐proline‐proline (TPP).METHODSWe validated new and existing antibodies against pT217, pT231, pT175, and pT181, then combined immunohistochemistry (IHC) and immunoassays (ELISA) to broadly examine the phosphorylation of the tau TPP motif in AD brains.RESULTSThe tau burden, as examined by IHC and ELISA, correlates to Braak stages across all TPP sites. Moreover, we observed regional variability across four TPP motif phosphorylation sites in multiple brains of sporadic AD patients.DISCUSSIONWe conclude that there is an elevation of TPP tau phosphorylation in AD brains as disease advances. The regional variability of pTPP tau suggests that examining different phosphorylation sites is essential for a comprehensive assessment of tau pathology.