Yun, Yejin Lee, Sang-Yeon Choi, Won Hoon Park, Jong-Chan Lee, Dong Han Kim, Yun Kyung Lee, Jung Hoon Lee, Jun-Young Lee, Min Jae Kim, Young Ho 2024-01-19T16:31:54Z 2024-01-19T16:31:54Z 2021-09-05 2020-10 1387-2877 https://pubs.kist.re.kr/handle/201004/118026 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 = 55) was measured with fluorogenic reporter substrate, suc-LLVY-AMC. To assess MCI, the Montreal Cognitive Assessmentwas conducted with a cut-off score of 22/23. All patients underwent audiological and psychoacoustic analyses. Levels of c-proteasomes, A beta(42), and A beta(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 A beta 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. English IOS PRESS CIRCULATING PROTEASOMES HEARING-LOSS WORKING-MEMORY 20S PROTEASOME MOUSE MODEL ALZHEIMERS RISK BETA TAU Proteasome Activity in the Plasma as a Novel Biomarker in Mild Cognitive Impairment with Chronic Tinnitus Article 10.3233/JAD-200728 1 JOURNAL OF ALZHEIMERS DISEASE, v.78, no.1, pp.195 - 205 JOURNAL OF ALZHEIMERS DISEASE 78 1 195 205 scie scopus 000582727600013 2-s2.0-85095111019 Neurosciences Neurosciences & Neurology Article CIRCULATING PROTEASOMES HEARING-LOSS WORKING-MEMORY 20S PROTEASOME MOUSE MODEL ALZHEIMERS RISK BETA TAU Amyloid-beta biomarker mild cognitive impairment plasma proteasome tinnitus