Accumulating evidence suggests that the propagation of hyperphosphorylation of tau protein and the amyloid-β peptide can be mediated by extracellular vesicles (EVs) and be associated with the onset and the progression of Alzheimer's disease (AD). As EVs may transfer between the brain and the blood, we have thus hypothesized that the total plasma EVs (pEVs) may contain potential markers to predict the mild cognitive impairment (MCI) and AD progression. We have thus quantified AD-related proteins in isolated pEVs from controls, MCI and AD subjects. In pEVs, we observed early changes of total tau (tTau), amyloid precursor protein levels, and phospho-tau (pTau)-T181/tTau ratio from MCI subjects and late increases of Aβ42 and pTau-T181 levels from patients with moderate AD. Interestingly, abnormal amyloid precursor protein levels and pTau-T181/tTau ratio in pEVs demonstrated a high accuracy to define MCI and AD staging. Although larger samples sizes will be needed to generate well-powered investigations, these preliminary results highlighted the potential of AD-related proteins enriched in pEVs as a sensitive tool for differentiating patients with MCI to patients with AD and monitoring AD progression.

中文翻译：

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轻度认知障碍和阿尔茨海默病进展过程中总循环细胞外囊泡中致病蛋白的分布

越来越多的证据表明，tau 蛋白和淀粉样蛋白 β 肽过度磷酸化的传播可以由细胞外囊泡 (EV) 介导，并且与阿尔茨海默病 (AD) 的发病和进展有关。由于 EVs 可能在大脑和血液之间转移，因此我们假设总血浆 EVs (pEVs) 可能包含预测轻度认知障碍 (MCI) 和 AD 进展的潜在标志物。因此，我们量化了来自对照、MCI 和 AD 受试者的分离 pEV 中的 AD 相关蛋白。在 pEV 中，我们观察到 MCI 受试者的总 tau (tTau)、淀粉样前体蛋白水平和磷酸-tau (pTau)-T181/tTau 比率的早期变化，以及中度 AD 患者 Aβ42 和 pTau-T181 水平的晚期增加。有趣的是，pEVs 中异常的淀粉样前体蛋白水平和 pTau-T181/tTau 比值证明了定义 MCI 和 AD 分期的高精度。尽管需要更大的样本量才能进行有力的研究，但这些初步结果强调了富含 pEV 的 AD 相关蛋白作为区分 MCI 患者与 AD 患者并监测 AD 进展的敏感工具的潜力。