Department of Neurology, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan.
Department of Zaitaku (Homecare) Medicine, Kyoto Prefectural University of Medicine, Kyoto, 602-0841, Japan.
Mol Neurodegener. 2017 Sep 4;12(1):63. doi: 10.1186/s13024-017-0206-8.
There is still a substantial unmet need for less invasive and lower-cost blood-based biomarkers to detect brain Alzheimer's disease (AD) pathology. This study is aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181) is informative in the diagnosis of AD.
We have developed a novel ultrasensitive immunoassay to quantify plasma p-tau181, and measured the levels of plasma p-tau181 in three cohorts.
In the first cohort composed of 20 AD patients and 15 age-matched controls, the plasma levels of p-tau181 were significantly higher in the AD patients than those in the controls (0.171 ± 0.166 pg/ml in AD versus 0.0405 ± 0.0756 pg/ml in controls, p = 0.0039). The percentage of the subjects whose levels of plasma p-tau181 exceeded the cut-off value (0.0921 pg/ml) was significantly higher in the AD group compared with the control group (60% in AD versus 16.7% in controls, p = 0.0090). In the second cohort composed of 20 patients with Down syndrome (DS) and 22 age-matched controls, the plasma concentrations of p-tau181 were significantly higher in the DS group (0.767 ± 1.26 pg/ml in DS versus 0.0415 ± 0.0710 pg/ml in controls, p = 0.0313). There was a significant correlation between the plasma levels of p-tau181 and age in the DS group (R = 0.4451, p = 0.0013). All of the DS individuals showing an extremely high concentration of plasma p-tau181 (> 1.0 pg/ml) were older than the age of 40. In the third cohort composed of 8 AD patients and 3 patients with other neurological diseases, the levels of plasma p-tau181 significantly correlated with those of CSF p-tau181 (R = 0.4525, p = 0.023).
We report for the first time quantitative data on the plasma levels of p-tau181 in controls and patients with AD and DS, and these data suggest that the plasma p-tau181 is a promising blood biomarker for brain AD pathology. This exploratory pilot study warrants further large-scale and well-controlled studies to validate the usefulness of plasma p-tau181 as an urgently needed surrogate marker for the diagnosis and disease progression of AD.
目前仍然存在对非侵入性和低成本的基于血液的生物标志物的巨大需求，以检测大脑阿尔茨海默病（AD）病理学。本研究旨在确定是否定量检测血浆中苏氨酸 181 位磷酸化的 tau（p-tau181）对 AD 的诊断有帮助。
我们开发了一种新的超灵敏免疫测定法来定量检测血浆 p-tau181，并在三个队列中测量了血浆 p-tau181 的水平。
在由 20 名 AD 患者和 15 名年龄匹配的对照者组成的第一队列中，AD 患者的血浆 p-tau181 水平明显高于对照组（AD 患者中为 0.171±0.166 pg/ml，对照组中为 0.0405±0.0756 pg/ml，p=0.0039）。AD 组中血浆 p-tau181 水平超过临界值（0.0921 pg/ml）的患者比例明显高于对照组（AD 组为 60%，对照组为 16.7%，p=0.0090）。在由 20 名唐氏综合征（DS）患者和 22 名年龄匹配的对照者组成的第二队列中，DS 组的血浆 p-tau181 浓度明显高于对照组（DS 组中为 0.767±1.26 pg/ml，对照组中为 0.0415±0.0710 pg/ml，p=0.0313）。DS 组中血浆 p-tau181 水平与年龄之间存在显著相关性（R=0.4451，p=0.0013）。所有表现出极高血浆 p-tau181 浓度（>1.0 pg/ml）的 DS 个体均大于 40 岁。在由 8 名 AD 患者和 3 名患有其他神经退行性疾病的患者组成的第三队列中，血浆 p-tau181 水平与 CSF p-tau181 水平显著相关（R=0.4525，p=0.023）。
我们首次报告了 AD 和 DS 患者及对照者血浆 p-tau181 水平的定量数据，这些数据表明血浆 p-tau181 是一种很有前途的大脑 AD 病理学的血液生物标志物。这项探索性的初步研究需要进一步进行大规模和对照良好的研究，以验证血浆 p-tau181 作为 AD 诊断和疾病进展的迫切需要的替代标志物的有用性。
