Investigating the impact of COVID-19 on Parkinson's disease

新冠肺炎的神经病理以特殊的神经免疫激活和星形细胞/小胶质细胞增多症和炎性信号增加为特征。SARS-CoV-2与基底节/脑干有亲和力，已被证明会影响神经系统，导致神经症状。尽管有单一病例报告称新冠肺炎患者在感染病毒后几周内出现帕金森症，但目前只有推测证据表明新冠肺炎与帕金森病之间存在联系。由于这种潜在的联系只有在未来几年或几十年才会变得明显，因此调查新冠肺炎是否以及如何影响帕金森病是有意义的。我们假设，研究新冠肺炎患者、新冠肺炎伴发帕金森病患者与帕金森病患者和对照组的大脑将告诉我们一个潜在的联系，并将揭开新冠肺炎调节的帕金森病中活跃的通路与生物标记物的相关性。我们假设新冠肺炎的神经免疫激活导致加速的神经退行性变。这项建议旨在比较使用和不使用新冠肺炎的PD患者和对照组的神经病理和扰动的生物通路，以了解这些机制。具体地说，我们将通过2a)全球RNA转录和2b)单细胞RNA测序在单细胞水平上研究1)跨大脑不同区域(皮质、纹状体、黑质、小脑)的神经免疫激活和蛋白质折叠/沉积和清除途径，以及2)在额叶皮质和中脑中差异表达的基因。最后，我们将整合所有有针对性的和全球性的方法来识别活跃在新冠肺炎/帕金森病和新冠肺炎中的生物通路，并评估获得的新冠肺炎后存活帕金森病患者的标志物谱的生物标志物潜力，以预测帕金森病的预后。通过深入探讨新冠肺炎与帕金森病之间是否存在关系，这一建议将让我们了解SARS-CoV-2感染构成发展或恶化的风险。

Neuropathology of COVID-19 is characterized by a peculiar neuroimmunological activation with astro/microgliosis and increased inflammatory signaling. SARS-CoV-2 has an affinity for the basal ganglia/brainstem and has been shown to affect the nervous system, causing neurological symptoms. Although there have been single case reports of COVID-19 patients having developed parkinsonism within weeks of contracting the virus, there is currently only speculative evidence for a link between COVID-19 and PD. Since this potential link will only become obvious in the coming years or decades, it is pertinent to investigate if and how COVID-19 impacts PD. We hypothesize that studying brains of COVID-19 patients, COVID-19 patients with concomitant PD as compared to PD patients and controls will inform us on a potential link and will unravel pathways active in COVID-19-modulated PD with biomarker relevance. We hypothesize that neuroimmunological activation in COVID-19 lead to accelerated neurodegeneration. This proposal aims to compare the neuropathology and perturbed biological pathways of PD patients and controls with and without COVID-19 to understand these mechanisms. Specifically, we will investigate 1) neuroimmune activation and protein folding/deposition and clearance pathways across different regions of the brain (cortex, striatum, substantia nigra, cerebellum) and 2) differentially expressed genes in frontal cortex and midbrain of the above-mentioned groups by 2a) global RNA transcriptomics and 2b) single-cell RNA sequencing to map disease-specific patterns on a single-cell level. Lastly, we will 3) integrate all targeted and global approaches to identify biological pathways active in COVID-19/PD and COVID-19 and assess biomarker potential of obtained marker profiles in living PD patients post COVID-19 to predict PD outcome. By thoroughly exploring whether there is a relationship between COVID-19 and PD, this proposal will inform us on the risk SARS-CoV-2 infections pose the development or worsening of.