Department of Neurodegeneration Diagnostics, Medical University of Białystok, 15-269 Białystok, Poland.
Department of Biochemical Diagnostics, University Hospital of Białystok, 15-269 Białystok, Poland.
Int J Mol Sci. 2019 Sep 20;20(19):4661. doi: 10.3390/ijms20194661.
Although the causative role of the accumulation of amyloid β 1-42 (Aβ42) deposits in the pathogenesis of Alzheimer's disease (AD) has been under debate for many years, it is supposed that the toxicity soluble oligomers of Tau protein (TauOs) might be also the pathogenic factor acting on the initial stages of this disease. Therefore, we performed a thorough search for literature pertaining to our investigation via the MEDLINE/PubMed database. It was shown that soluble TauOs, especially granular forms, may be the most toxic form of this protein. Hyperphosphorylated TauOs can reduce the number of synapses by missorting into axonal compartments of neurons other than axon. Furthermore, soluble TauOs may be also responsible for seeding Tau pathology within AD brains, with probable link to AβOs toxicity. Additionally, the concentrations of TauOs in the cerebrospinal fluid (CSF) and plasma of AD patients were higher than in non-demented controls, and revealed a negative correlation with mini-mental state examination (MMSE) scores. It was postulated that adding the measurements of TauOs to the panel of CSF biomarkers could improve the diagnosis of AD.
虽然淀粉样β 1-42 (Aβ42) 沉积在阿尔茨海默病 (AD) 发病机制中的因果作用多年来一直存在争议，但推测 Tau 蛋白 (Tau) 的可溶性寡聚物毒性也可能是作用于这种疾病初始阶段的致病因素。因此，我们通过 MEDLINE/PubMed 数据库对与我们的研究相关的文献进行了全面检索。结果表明，可溶性 TauOs，特别是颗粒形式，可能是这种蛋白质毒性最大的形式。过度磷酸化的 TauOs 可能会通过错误分拣到神经元的轴突以外的轴突隔室而减少突触数量。此外，可溶性 TauOs 也可能负责在 AD 大脑中引发 Tau 病理学，可能与 AβOs 毒性有关。此外，AD 患者的脑脊液 (CSF) 和血浆中的 TauOs 浓度高于非痴呆对照组，并且与简易精神状态检查 (MMSE) 评分呈负相关。有人推测，将 TauOs 的测量添加到 CSF 生物标志物的面板中可以改善 AD 的诊断。
