Objective: This study aims to identify differentially expressed salivary miRNAs and validate the diagnostic potential for idiopathic Parkinson's disease (PD). Also, the disease specificity of candidate miRNAs was evaluated between PD, multiple system atrophy (MSA), and essential tremor (ET).Methods: We collected salivary samples from 50 PD, 20 ET, and 20 MSA patients, as well as 30 healthy controls (HCs). In the discovery phase, salivary miRNA microarray analysis was performed. In-silico analysis was used to investigate the target genes of differentially expressed miRNAs and clustered pathways. In validation phase, RT-qPCR was performed with samples from 30 PD patients and 30 HCs. Subsequently, we investigated candidate miRNAs in all recruited subjects. Receiver operating characteristic curve and Spearman correlation analysis was performed to determine diagnostic usefulness.Results: We identified 43 miRNAs that were differentially expressed between 5 PD patients and 5 HCs by miRNA microarray analysis. Computational analysis revealed the target genes were clustered in the pathways associated with ubiquitin protein ligase activity. The result of RT-qPCR showed that the miR-29a-3p and miR-29c-3p were found to be significantly downregulated (p = 0.004, p = 0.027), whereas the miR-6756-5p was significantly upregulated in 30 PD patients compared with 30 HCs (p = 0.032). The miR-29a-3p expression level in PD patients was significantly lower than ET patients (p = 0.035), but higher than MSA patients (p < 0.0001). The diagnostic efficacy reached a little higher when the combination of miR-29a-3p and miR-29c-3p.Conclusion: The miRNA combination of salivary miR-29a-3p and miR-29c-3p has potential to be a diagnostic biomarker for idiopathic PD.

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Background Aggregation of α‐synuclein (oligomeric α‐syn) has been considered as the pathological hallmark of Parkinson's disease (PD) and multiple system atrophy (MSA). Studies showed oligomeric α‐syn/total α‐syn ratio was increased in the saliva of patients with PD, suggesting that seeding activity of salivary oligomeric α‐syn may be a novel biomarker for the diagnosis of PD and MSA. Objective This study aimed to evaluate the diagnostic value of salivary α‐syn seeding activity in patients with PD and MSA. Methods A total of 75 patients with PD, 18 patients with MSA, and 36 nonneurodegenerative healthy control subjects underwent salivary α‐syn real‐time quaking‐induced conversion (RT‐QuIC) assay. Results Salivary α‐syn RT‐QuIC assay distinguished patients with PD with 76.0% sensitivity (95% confidence interval [CI], 66.1–85.9) and 94.4% specificity (95% CI, 86.6–100.0). RT‐QuIC assay sensitivity reached 61.1% (95% CI, 36.2–86.1) in patients with MSA. No significant differences were observed in the diameter of salivary α‐syn fibrils examined by electron microscopy and in thioflavin T fluorescence intensity of salivary α‐syn fibrils detected by RT‐QuIC assay between patients with PD and MSA. Notably, the lag phase of RT‐QuIC assay from patients with PD was significantly shorter than that of patients with MSA, which might be clinically applicable to the discrimination between PD and MSA. Conclusions Salivary α‐syn seeding activity may serve as a novel biomarker for the clinical diagnosis of PD and MSA.© 2022 International Parkinson and Movement Disorder Society © 2022 International Parkinson and Movement Disorder Society

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Neurological complications have emerged as a significant cause of morbidity and mortality in the ongoing COVID-19 pandemic. In this focused review, we summarize evidence of the neuroinvasiveness, neurotropism and neurovirulence of the novel beta coronavirus SARS-CoV-2. Potential means of neuroinvasion include hematogenous spread, neuronal retrograde transport from the vagus or olfactory nerves and the transcribrial route. Pathologic studies suggest direct neuroinvasion via hematogenous spread and retrograde transport by the olfactory nerve, while retrograde transport through the vagus and olfactory nerves remains hypothetical. Experimental evidence confirms that angiotensin converting enzyme 2 (ACE2) is the main receptor for SARS-CoV-2, suggesting this ACE2 as a target of neurotropism. Direct evidence of detection of the virus in cerebral spinal fluid or post-mortem brain tissue is sparse. There is a paucity of reported post-mortem neuropathological examinations in victims of COVID-19, highlighting the importance of accruing additional cases. The potential for long-term neurological consequences of COVID-19 signals the importance of continued surveillance for neuroimmune disorders and neurodegenerative in those infected by SARS-CoV-2.