Tau蛋白异常磷酸化是AD病理机制领域的热点和难点问题，同病异证生物学机制是中医学证候实质研究的关键科学问题，本项目将两个领域中热点和关键科学问题结合，以期从tau蛋白异常磷酸化机制角度深化AD疾病病理机制并阐明该病肾虚证、痰浊证、血瘀证在蛋白水平的同病异证微观机制, 为今后中药复方有效成分的筛选标示出较为明确的靶点指向，为3个证候的诊断标准提供微观指标参考。课题组前期研究发现3个证候tau蛋白过度磷酸化在Thr205、Thr181、Ser231位点上存在明显差异。本项目以此为基础选取full moon 广谱磷酸化蛋白芯片，确认和探索AD病3个典型证候tau蛋白异常磷酸化位点及其通路和相关蛋白。采用蛋白印迹、免疫荧光等技术检测所有蛋白通路结果，验证每个证候的位点及敏感通路，确定其显著特异性位点及蛋白通路，揭示其tau蛋白异常磷酸化机制。最后采用蛋白过表达或敲除模拟构建AD病证结合细胞模型。

Abnormal phosphorylation of tau protein is a central and difficult issue in the field of Alzheimer's disease pathology, the biological mechanism of the same disease with different syndromes is the key scientific issue which in essence study of Chinese Medicine syndrome, this project combines with two fields of central issue and critical scientific issue in order to deepen the pathogenesis of AD from the perspective of mechanism of tau phosphorylation and to clarify the microscopic mechanism of the same disease in different syndromes in protein standard with the syndrome of kidney deficiency, the syndrome of phlegm and the syndrome of blood stasis, so it can select and mark out more specific target point for the active ingredients of Chinese herbal formula in future, and can provide microeconomic indicators for diagnostic criteria of the three syndromes .As the basis ,our project choose the full moon broad spectrum of phosphorylated protein chip to identify and explore abnormal tau protein phosphorylation sites and pathways and related proteins of three typical syndromes of AD. Using the technology of Western blot and immunofluorescence to detect protein pathway, verify each syndromes sensitive pathway, determine its remarkable specificity protein pathway and reveal abnormal tau protein phosphorylation mechanism. Finally, using protein overexpression or knockdown and other methods to construct AD disease cell model of the three syndromes combined of disease and syndrome.