Kellett Katherine A B, Hooper Nigel M
Institute of Brain, Behaviour and Mental Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, M13 9PT, UK,
Subcell Biochem. 2015;76:363-74. doi: 10.1007/978-94-017-7197-9_17.
Tissue non-specific alkaline phosphatase (TNAP) is present on neuronal membranes and induces neuronal toxicity via tau dephosphorylation; a mechanism which could play a role in the neuronal loss seen in Alzheimer's disease (AD). TNAP increases in the plasma following brain injury and cerebrovascular disease. In this chapter we summarise our previous work which looked at changes in TNAP activity in the brain and plasma of AD individuals and discuss whether these changes may be reflective of neuronal loss. Our data demonstrate that TNAP activity is significantly increased in the brain in both the sporadic and familial forms of AD and that TNAP activity is significantly increased in the plasma in AD patients. In addition, we describe a significant inverse correlation between plasma TNAP activity and cognitive function in AD. Using these data we propose a model for TNAP-induced neurodegeneration in AD resulting from tau dephosphorylation following secretion of tau from neuronal cells.
组织非特异性碱性磷酸酶（TNAP）存在于神经元膜上，并通过tau蛋白去磷酸化诱导神经元毒性；这一机制可能在阿尔茨海默病（AD）中出现的神经元丢失中起作用。脑损伤和脑血管疾病后血浆中TNAP会升高。在本章中，我们总结了我们之前的工作，该工作研究了AD患者大脑和血浆中TNAP活性的变化，并讨论了这些变化是否可能反映神经元丢失。我们的数据表明，散发性和家族性AD患者大脑中的TNAP活性均显著升高，且AD患者血浆中的TNAP活性也显著升高。此外，我们描述了AD患者血浆TNAP活性与认知功能之间存在显著的负相关。利用这些数据，我们提出了一个AD中TNAP诱导神经退行性变的模型，该模型是由神经元细胞分泌tau蛋白后tau蛋白去磷酸化导致的。
