Objective: To determine the diagnostic value of circulating miRNAs and the extracellular vesicle proteins for early detection of patients with Parkinson’s disease and mild cognitive impairment  and PD patients with dementia.

Background: Parkinson’s disease is a progressive neurodegenerative disorders with motor and non-motor disability. A significant portion of PD Patients developed to PDMCI or PDD  with a profound reduced quality of life and higher mortality. Currently, the only clinical tool for cognition evaluation is a complex, time consuming neuropsychological test which halts its accessibility in clinical practice. Therefore, searching for reliable and accessible biomarkers discriminating PD, PD-MCI and PDD are crucial.

Method: In an initiating cohort, small RNAs in the plasma from the subjects, including 19 PDND, 7 PDMCI, 17 PDD, and 21 healthy control (HC), were included from the Movement disorder clinic of NTUH for sequenced and profiled. Significantly changed miRNAs in PD-MCI and PDD were selected for heatmap analysis and for the model construction. The resulting receiver operating characteristic (ROC) curve has validated the diagnostic ability of these candidate miRNAs as in combination or using single miRNA alone. Additionally, we also isolated exosome-enriched EVs derived from the plasma of PD patients, subjected to the proteomic analysis with high-resolution LC-Mass spectrometry, including 21 PD, 8 PD-MCI, 20 PDD and 21 HC.

Results: Plasma miR-5698, miR-135b-3p, miR-7975 , miR-514a-5p, miR-486-3p , miR-4668-3p, miR-659-5p were selected as candidate miR to differentiating PDND from PD-MCI and PDD. The resulting ROC curve was applied to validate the diagnostic ability of these candidate miRNAs as in combination (AUC = 0.703) or using single miRNA alone (miR-4668-3p, ACU = 0.756; miR-7975, AUC = 0.712). Moreover, we have verified that a candidate EV protein, TAOK1 which is upregulated in PD-MCI and PDD has a reverse correlation with the cognitive condition of PD patients (Pearson r = -0.4549).

Conclusion: In this study, we validate the candidate plasma miRNAs for the differential diagnosis of PDND, PDMCI and PDD. TAOK1 upregulated in PD-MCI and PDD might be related to tau protein pathology. Beyond biomarker discovery, findings from the study may merit as a clue that small non-coding RNAs and EV proteins are involved in the etiology of PD-associated cognitive impairment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/candidate-plasma-mirnas-and-ev-protein-as-novel-biomarkers-in-parkinsons-disease-patients-with-cognitive-impairment-and-dementia/