1.Prasinezumab slows motor progression in rapidly progressing early-stage Parkinson's disease

DOI: 10.1038/s41591-024-02886-y

https://www.nature.com/articles/s41591-024-02886-y

Prasinezumab, a monoclonal antibody targeting aggregated α-synuclein, was studied in early-stage Parkinson's disease (PD) but didn't meet its primary endpoint in the PASADENA phase 2 trial. However, exploratory analysis showed slower motor signs progression in prasinezumab-treated patients, particularly in subgroups with faster progression. These subgroups included those with rapid eye movement sleep behavior disorder, higher disease severity, and specific motor subphenotypes. While suggestive of potential benefits in rapidly progressing PD, this analysis was post hoc, necessitating further randomized trials for validation. Prasinezumab might offer greater efficacy in slowing motor decline in PD patients with more aggressive disease progression, but additional research is required to confirm these findings.

2.Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease

DOI: 10.1038/s41467-024-47552-6

https://www.nature.com/articles/s41467-024-47552-6

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease generates evoked resonant neural activity (ERNA), a high-frequency oscillation linked to treatment effectiveness. This study investigates ERNA's neuronal and synaptic origins, suggesting it represents a subcortical neural circuit signature of DBS-mediated basal ganglia indirect pathway engagement. Key findings include: (i) Each ERNA peak correlates with STN neuronal inhibition; (ii) ERNA's temporal dynamics are characterized; (iii) An in silico model reveals necessary synaptic dynamics for ERNA emergence; (iv) ERNA is localized to the dorsal STN; (v) Patient-specific hotspot locations are used to evaluate ERNA's spatial relevance to DBS outcomes; and (vi) Local fiber activation profiles linked to group-level ERNA hotspot are delineated. These insights advance understanding of DBS mechanisms and treatment optimization in Parkinson's disease.

3.A single-nuclei paired multiomic analysis of the human midbrain reveals age- and Parkinson's disease-associated glial changes

DOI: 10.1038/s43587-024-00583-6

https://www.nature.com/articles/s43587-024-00583-6

This study investigates the impact of aging on gene expression and chromatin accessibility in the brain, particularly focusing on Parkinson's disease (PD). Analyzing single-nuclei multiomic data from midbrain samples, researchers found age-related changes in all glial cell types, with microglia and oligodendrocytes further altered in PD. Evidence suggests a disease-associated oligodendrocyte subtype and identifies genes lost during aging and disease progression, such as CARNS1, potentially predisposing cells to disease phenotypes. Surprisingly, chromatin accessibility remains relatively stable across aging and PD within cell types. However, peak-gene associations are significantly altered, revealing cell-type-specific chromosomal loci containing PD-associated single-nucleotide polymorphisms. This study uncovers a novel role for oligodendrocytes in aging and PD pathogenesis.

4.Diet and the gut microbiome in patients with Parkinson's disease

DOI: 10.1038/s41531-024-00681-7

https://www.nature.com/articles/s41531-024-00681-7

This study investigates the relationship between diet, gut microbiome composition, and predicted functional pathways in Parkinson's disease (PD) patients. Fecal samples from 85 PD patients were analyzed using 16S rRNA gene sequencing, while diet quality was assessed using the Healthy Eating Index 2015 (HEI-2015). Results show that higher HEI scores and fiber intake correlate with increased levels of anti-inflammatory bacteria like Butyricicoccus and Coprococcus 1, while higher added sugar intake is associated with pro-inflammatory bacteria such as Klebsiella. Predictive metagenomics suggest that a healthy diet and fiber intake reduce bacterial genes linked to lipopolysaccharide biosynthesis, potentially reducing neuroinflammation. This study highlights the impact of diet on the gut microbiome in PD, suggesting that a healthy diet may mitigate PD risk and progression through its effects on gut microbiota.

5.Eye movement function captured via an electronic tablet informs on cognition and disease severity in Parkinson's disease

https://www.nature.com/articles/s41598-024-59750-9

This study explores the utility of tablet-based eye tracking in assessing cognitive abilities and disease severity in Parkinson's Disease (PD). Tablet-based eye tracking offers a cost-effective and reliable method for measuring oculomotor parameters. Results demonstrate that oculomotor measures can explain up to 71% of cognitive test score variance, such as the Trail Making Test. Additionally, a support vector classifier using eye-tracking parameters accurately distinguishes between mild and moderate PD with 90% accuracy based on UPDRS scores. These findings suggest that tablet-based eye tracking has potential for rapidly scaling oculomotor assessment in both research and clinical settings, providing insights into disease progression and cognitive function in PD.