Kolarova Michala, Sengupta Urmi, Bartos Ales, Ricny Jan, Kayed Rakez
National Institute of Mental Health, Klecany, Czech Republic.
Third Faculty of Medicine, Charles University, Prague, Czech Republic.
J Alzheimers Dis. 2017;58(2):471-478. doi: 10.3233/JAD-170048.
Although tau protein was long regarded as an intracellular protein with several functions inside the cell, new evidence has shown tau secretion into the extracellular space. The active secretion of tau could be a physiological response of neurons to increased intracellular amounts of tau during the progression of tau pathology. We looked for potential differences in the serum levels of toxic tau oligomers in regards to cognitive impairment of subjects. We detected tau oligomers in the serum of Alzheimer's disease (AD) patients, but they were also present to some extent in the serum of healthy older subjects where the levels positively correlated with aging (Spearman r = 0.26, p = 0.016). On the contrary, we found lower levels of tau oligomers in the serum of mild cognitive impairment (MCI) (p = 0.033) and MCI-AD (p = 0.006) patients. These results could suggest that clearance of extracellular tau proteins takes place, in part, in the periphery. In the case of MCI patients, the lower levels of tau oligomers could be the result of impaired clearance of tau protein from interstitium to blood and consequent accumulation of tau aggregates in the brain.
尽管长期以来tau蛋白被视为一种在细胞内具有多种功能的细胞内蛋白，但新证据表明tau蛋白可分泌到细胞外空间。在tau病理进展过程中，tau蛋白的主动分泌可能是神经元对细胞内tau蛋白量增加的一种生理反应。我们研究了有毒tau寡聚体血清水平与受试者认知障碍之间的潜在差异。我们在阿尔茨海默病（AD）患者的血清中检测到了tau寡聚体，但在健康老年受试者的血清中也有一定程度的存在，其水平与衰老呈正相关（斯皮尔曼相关系数r = 0.26，p = 0.016）。相反，我们发现轻度认知障碍（MCI）患者（p = 0.033）和MCI-AD患者（p = 0.006）血清中的tau寡聚体水平较低。这些结果可能表明细胞外tau蛋白的清除部分发生在外周。对于MCI患者，tau寡聚体水平较低可能是tau蛋白从间质到血液的清除受损以及tau聚集体在大脑中积累的结果。
