Han Pengcheng, Serrano Geidy, Beach Thomas G, Caselli Richard J, Yin Junxiang, Zhuang Ningning, Shi Jiong
Barrow Neurological Institute, St Joseph's Hospital and Medical Center, Phoenix, Arizona, USA.
Department of Pathology and Laboratory Medicine Residency Program, Medical University of South Carolina, Charleston, South Carolina, USA.
J Neuropathol Exp Neurol. 2017 Jan 1;76(1):44-51. doi: 10.1093/jnen/nlw105.
Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor. Our results suggest that the increase in NFT in AD is likely attributable to post-translational processes; the increase in CSF tau in AD patients is due to an accelerated carrier-based secretion. Moreover, cognitive dysfunction assessed by final Mini-Mental State Examination scores correlated with the secretion factor but not with the soluble tau.
神经原纤维缠结（NFTs）是阿尔茨海默病（AD）患者大脑中不溶性tau蛋白的产物。脑脊液（CSF）tau水平是AD诊断中的一种生物标志物。脑实质中tau蛋白的可溶性部分可能是CSF tau的来源，但此前尚未对此进行量化。我们在尸检时测量了7名认知正常、12名轻度认知障碍和19名AD受试者颞叶和额叶脑组织样本中的CSF tau和可溶性脑tau。基于测得的脑可溶性tau，我们计算了全脑tau负荷并估计了tau分泌因子。我们的结果表明，AD中NFT的增加可能归因于翻译后过程；AD患者CSF tau的增加是由于基于载体的分泌加速。此外，通过最终简易精神状态检查评分评估的认知功能障碍与分泌因子相关，但与可溶性tau无关。
