Proteasome Activity in the Plasma as a Novel Biomarker in Mild Cognitive Impairment with Chronic Tinnitus

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.