Abstract

Background:

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.

Objective:

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.

Methods:

c-Proteasome activity in the plasma of tinnitus patients (N = 56) 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, Aβ ₄₂, and Aβ ₄₀ were measured using ELISA, and their association with c-proteasome activity was evaluated.

Results:

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.

Conclusion:

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.

中文翻译：

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血浆中的蛋白酶体活性作为慢性耳鸣轻度认知障碍的新型生物标志物。

摘要

背景：

尽管之前已经报道了人类血液中存在蛋白酶体，称为循环蛋白酶体（c-蛋白酶体），但它们的起源和病理生理学功能在很大程度上仍然未知。

客观的：

鉴于阿尔茨海默病模型小鼠的 c-蛋白酶体活性显着降低，并且老年患者的轻度认知障碍 (MCI) 频率相对较高，并伴有慢性耳鸣，我们研究了人血浆中的 c-蛋白酶体活性是否与认知功能有关。慢性耳鸣患者。

方法：

耳鸣患者（N = 56）血浆中的 c-蛋白酶体活性用荧光报告底物 suc-LLVY-AMC 测量。为了评估 MCI，蒙特利尔认知评估的截止分数为 22/23。所有患者都接受了听力学和心理声学分析。使用 ELISA 测量c-蛋白酶体、A β ₄₂和 A β _{40 的}水平，并评估它们与 c-蛋白酶体活性的关联。

结果：

慢性耳鸣和 MCI 患者循环蛋白酶体的活性显着降低 ( p  = 0.042)，而其他血浆酶的活性几乎没有相关性。此外，C-蛋白酶体活性呈负的血浆A中的电平相关联β并且是直接依赖于患者的慢性耳鸣的血浆中其自身的浓度。

结论：

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，在 MCI 诊断的背景下提出了一种新型的非侵入性生物标志物。