Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Bundang Hospital, Seoul, Korea.
J Alzheimers Dis. 2020;78(1):195-205. doi: 10.3233/JAD-200728.
Although the existence of proteasomes in human blood, termed circulating proteasomes (c-proteasomes), has been reported previously, their origin and pathophysiological functions remain largely unknown.
Given that c-proteasome activity was significantly reduced in Alzheimer's disease model mice and relatively high frequency of mild cognitive impairment (MCI) is accompanied by chronic tinnitus in aged patients, we examined whether c-proteasome activity in human plasma was associated with cognitive function in patients with chronic tinnitus.
c-Proteasome activity in the plasma of tinnitus patients (N = 55) was measured with fluorogenic reporter substrate, suc-LLVY-AMC. To assess MCI, the Montreal Cognitive Assessment was conducted with a cut-off score of 22/23. All patients underwent audiological and psychoacoustic analyses. Levels of c-proteasomes, Aβ42, and Aβ40 were measured using ELISA, and their association with c-proteasome activity was evaluated.
The activity of circulating proteasomes was significantly lower in patients with chronic tinnitus and MCI (p = 0.042), whereas activities of other plasma enzymes showed little correlation. In addition, c-proteasome activity was negatively associated with the level of plasma Aβ and was directly dependent on its own concentration in the plasma of patients with chronic tinnitus.
Our current work provides a new perspective for understanding the potential relationship between circulating proteasomes in the plasma and cognitive dysfunction, suggesting a novel, non-invasive biomarker in the context of MCI diagnosis.
虽然先前已有报告称人类血液中存在蛋白酶体，称为循环蛋白酶体（c-proteasomes），但其起源和病理生理学功能仍知之甚少。
鉴于阿尔茨海默病模型小鼠中的 c-proteasome 活性显著降低，且年龄较大的慢性耳鸣患者中轻度认知障碍（MCI）的相对高发频率，我们研究了人类血浆中的 c-proteasome 活性是否与慢性耳鸣患者的认知功能有关。
使用荧光报告底物 suc-LLVY-AMC 测定耳鸣患者（N=55）血浆中的 c-proteasome 活性。为了评估 MCI，采用蒙特利尔认知评估，以 22/23 的截断值进行。所有患者均进行了听力和心理声学分析。采用 ELISA 测定血浆中的 c-proteasomes、Aβ42 和 Aβ40 水平，并评估其与 c-proteasome 活性的相关性。
慢性耳鸣伴 MCI 患者的循环蛋白酶体活性显著降低（p=0.042），而其他血浆酶的活性相关性较小。此外，c-proteasome 活性与血浆 Aβ水平呈负相关，并且直接依赖于慢性耳鸣患者血浆中的自身浓度。
我们目前的工作为理解血浆中循环蛋白酶体与认知功能障碍之间的潜在关系提供了新的视角，提示在 MCI 诊断中存在一种新的、非侵入性的生物标志物。
