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Open science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities, thus we coordinated a virtual 3-day hackathon event, during which 49 early-career scientists from 12 countries built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools. Each team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools. Hackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early-career researchers. The resources generated can be used to accelerate research on the genetics of PD.

Background: Isolated REM sleep behavior disorder (iRBD) is known to be an early feature in some people with PD. Early motor anomalies may also be prodromes of PD. Standardized protocols, including quantitative motor tools for their measurement, are yet to be determined. Methods: A set of quantitative motor tests was used to compare iRBD patients with controls. These included two online keyboard-based tests, the BRadykineisa Akinesia INcoordination (BRAIN) test and the Distal Finger Tapping (DFT) test, a timed handwriting task and two separate motor assessments (10-meter walking and finger tapping) carried out both alone and during a mental (dual) task. This battery was compared with the motor section of the MDS-MDS-UPDRS-III. ROC analyses were used to measure diagnostic accuracy. Results: We included 33 patients with video-PSG-confirmed iRBD (68.88 years; SD 8.07) and 29 age and sex matched controls. The iRBD group performed the alternate tapping task (BRAIN test) and single finger tapping task (DFT test) more slowly (p<0.001 and p=0.020 respectively) and erratically (p<0.001 and p=0.009 respectively) than controls. Handwriting speed was on average 10 seconds slower in the iRBD compared with controls (p=0.004). Unlike controls, dual tasking unmasked motor deficits in the iRBD group with patients having a slower walking pace (p<0.001) and smaller amplitude (p=0.001) with slower finger tapping and (p=0.007) than when the task was done in isolation. The combination of BRAIN & DFT tests with the effect of dual tasking on walking and finger tapping performance gave the overall accuracy of 90.3% sensitivity for 89.3% specificity (AUC 0.94 (95% CI 0.88 to 0.99)), which was substantially higher than the accuracy of the MDS-UPDRS-III (minus action tremor) (69.7% sensitivity for 72.4% specificity and AUC 0.81, 95% CI 0.71 to 0.91) for detecting motor abnormalities. Conclusion: The tests used in this study were able to detect early patterns of motor dysfunction that are not included in standardized clinical scales. Keyboard tapping was found to be slow and erratic in people with iRBD. Dual tasks unmasked hypokinetic finger tapping and slower walking pace. This study suggests that speed, incoordination, and dual task motor deterioration might be potential indicators of incipient PD in iRBD.

BackgroundOpen science and collaboration are necessary to facilitate the advancement of Parkinson’s disease (PD) research. Hackathons are collaborative events that bring together people with different skill sets and backgrounds to generate resources and creative solutions to problems. These events can be used as training and networking opportunities.ObjectiveTo coordinate a virtual hackathon to develop novel PD research tools.Methods49 early career scientists from 12 countries collaborated in a virtual 3-day hackathon event in May 2021, during which they built tools and pipelines with a focus on PD. Resources were created with the goal of helping scientists accelerate their own research by having access to the necessary code and tools.ResultsEach team was allocated one of nine different projects, each with a different goal. These included developing post-genome-wide association studies (GWAS) analysis pipelines, downstream analysis of genetic variation pipelines, and various visualization tools.ConclusionHackathons are a valuable approach to inspire creative thinking, supplement training in data science, and foster collaborative scientific relationships, which are foundational practices for early career researchers. The resources generated can be used to accelerate research on the genetics of PD.

Lewy body dementia (LBD) is a syndrome that is closely related to Parkinson disease (PD) and defined by cognitive decline, either preceding motor symptoms of PD À dementia with Lewy bodies (DLB), or after PD symptoms À Parkinson's disease dementia (PDD). Neuroinflammation has been postulated as a driver of α-synuclein aggregation, 1 a hallmark of LBD. However, most data on neuroinflammation in LBD/PD spectrum disorders have been derived from peripheral blood or post-mortem studies 2,3 and an in vivo mechanistic link has not yet been demonstrated.Gate et al investigated the neuroinflammation pathway in vivo by analyzing cerebrospinal fluid (CSF) from patients with LBD (DLB and PDD), healthy controls, and PD patients without cognitive impairment. Using single cell RNA and T-cell receptor sequencing, the authors identified a transcriptionally altered clonal CD4 + T cell population in the CSF of patients with LBD. Novel findings from this study were that the C-X-C motif chemokine receptor 4 (CXCR4) and the gene expressed by pro-inflammatory-producing T helper 17 (Th17) cells were highly expressed in these CD4 + cells. The ligand for CXCR4 was also highly expressed in patients with LBD both in the CSF and the cerebrovascular endothelial cells, suggesting central nervous system (CNS) recruitment of the clonal CD4 + population. Immunohistochemistry confirmed previous findings that CD3 + T cells enclose α-synuclein deposits. CSF CXCR4 ligand levels were also found to correlate with neurofilament light chain levels in patients with LBD. This implies that dysregulation of the CXCR4 pathway, previously implicated in multiple sclerosis and cancer, 4 is also associated with neurodegeneration in LBD. Finally, the authors detected a higher expression of IL-17A in CD3 + T cells stimulated with α-synuclein, implicating Th17 cells in dopaminergic cell death via the proinflammatory cytokine IL-17A in LBD patients. One limitation of this study was that direct interaction between the CSF clonal CD4 + and intraparenchymal CD3 + populations was not demonstrated.In summary, Gate et al propose a CNS autoimmune response as the basis for LBD pathogenesis. Influencing the CXCR4 pathway could therefore slow progression towards dementia in PD and could display disease-modifying effects in DLB. New CXCR4 antagonists have recently been approved for clinical trials. 5 Future studies focusing on the CXCR4 pathway should assess the proposed therapeutic agent for the ability to penetrate the blood-brain barrier, as well as establish the best stage for drug trials in LBD. Furthermore, clinically relevant markers of progression and target engagement will be essential for future drug trials in LBD.