PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD), a serious neurodegenerative disease, is pathologically characterized by synaptic loss and dysfunction. Synaptic vesicle protein 2A (SV2A) is an indispensable vesicular protein specifically expressed in synapses and can be used as a biomarker for synaptic density. We found that the expression of SV2A was down-regulated in the hippocampus of AD patients, yet the relation of SV2A to other hallmarks of AD pathology such as amyloid precursor protein (APP), β-amyloid (Aβ), and Tau protein is not thoroughly clear. In addition, SV2A colocalized with APP and was down-regulated at Aβ deposition. Moreover, we found that SV2A deficiency leads to a simultaneous increase in Aβ and Tau hyperphosphorylation, while SV2A overexpression was associated with downregulation of β-site APP cleaving enzyme 1 and apolipoprotein E genes. In addition, evidence gained in the study points to the phosphatidylinositol 3-kinase signaling pathway as a possible mediator in SV2A regulation influencing the incidence and development of AD. With limited effective diagnostic methods for AD, a close interplay between SV2A and AD-related proteins demonstrated in our study may provide novel and innovative diagnostic and therapeutic opportunities.
摘要：
阿尔茨海默病（AD），严重的神经退行性疾病,病理特征为突触丢失和功能障碍。突触囊泡蛋白2A(SV2A)是突触中不可缺少的特异性表达的囊泡蛋白,可作为突触密度的生物标志物。我们发现SV2A在AD患者海马中表达下调,然而，SV2A与AD病理的其他标志如淀粉样前体蛋白（APP）的关系，β-淀粉样蛋白(Aβ),和Tau蛋白不完全清楚。此外,SV2A与APP共定位，在Aβ沉积时下调。此外，我们发现SV2A缺乏导致Aβ和Tau过度磷酸化同时增加，而SV2A过表达与β位点APP裂解酶1和载脂蛋白E基因的下调有关。此外,研究中获得的证据表明,磷脂酰肌醇3-激酶信号通路可能是SV2A调节中影响AD发生和发展的介质.由于AD的有效诊断方法有限，我们的研究表明,SV2A和AD相关蛋白之间的密切相互作用可能提供新颖和创新的诊断和治疗机会.
