Plasma tau/amyloid-β1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer's disease
Plasma tau/amyloid-β1-42 ratio predicts brain tau deposition and neurodegeneration in Alzheimer's disease
复制标题
DOI：
10.1093/brain/awy347
复制
发表时间：
2019-03-01
期刊：
影响因子：
14.5
通讯作者：
Mook-Jung, Inhee
中科院分区：
文献类型：
--
作者：
Park, Jong-Chan;Han, Sun-Ho;Mook-Jung, Inhee
阿尔茨海默病的特征之一是脑中tau蛋白的异常沉积。虽然血浆tau已被提出作为阿尔茨海默病的潜在生物标志物，但与tau脑沉积的直接联系有限。在这里，我们通过PET成像估计了脑中体内tau沉积的量，并测量了总tau（t-tau）、磷酸化tau（p-tau，T181）和淀粉样蛋白-β（1-42）的血浆水平。我们发现血浆p-tau、t-tau、p-tau/淀粉样蛋白-β（1-42）和t-tau/淀粉样蛋白-β（1-42）与脑tau沉积以横截面和纵向方式显著相关。特别地，血浆中的t-tau/淀粉样蛋白-β（1-42）高度预测脑tau沉积，表现出80%的灵敏度和91%的特异性。有趣的是，血浆t-tau/淀粉样蛋白-β（1-42）与脑tau相关的脑区域与阿尔茨海默病中神经元缠结的典型沉积部位相似。此外，脑淀粉样蛋白沉积、脑葡萄糖代谢和海马体积变化的纵向变化也与血浆t-tau/淀粉样蛋白-β高度相关（1-42）。这些结果表明，血浆tau和淀粉样蛋白-β（1-42）水平的组合可能是预测脑tau病理学和神经变性的潜在生物标志物。
One of the hallmarks of Alzheimer's disease is abnormal deposition of tau proteins in the brain. Although plasma tau has been proposed as a potential biomarker for Alzheimer's disease, a direct link to brain deposition of tau is limited. Here, we estimated the amount of in vivo tau deposition in the brain by PET imaging and measured plasma levels of total tau (t-tau), phosphorylated tau (p-tau, T181) and amyloid-beta(1-42). We found significant correlations of plasma p-tau, t-tau, p-tau/amyloid-beta(1-42), and t-tau/amyloid-beta(1-42) with brain tau deposition in cross-sectional and longitudinal manners. In particular, t-tau/amyloid-beta(1-42) in plasma was highly predictive of brain tau deposition, exhibiting 80% sensitivity and 91% specificity. Interestingly, the brain regions where plasma t-tau/amyloid-beta(1-42) correlated with brain tau were similar to the typical deposition sites of neurofibrillary tangles in Alzheimer's disease. Furthermore, the longitudinal changes in cerebral amyloid deposition, brain glucose metabolism, and hippocampal volume change were also highly associated with plasma t-tau/amyloid-beta(1-42). These results indicate that combination of plasma tau and amyloid-beta(1-42) levels might be potential biomarkers for predicting brain tau pathology and neurodegeneration.