Next generation histology methods for three-dimensional imaging of fresh and archival human brain tissues

Current available tissue clearing techniques are mostly used for rodent tissues. Here, the authors develop OPTIClear solution for fresh and archival human brain tissue clearing and establish associated protocols for three-dimensional histological investigations

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer's disease and Parkinson's disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition

Clinical trials for cognition in Parkinson's disease: Where are we and how can we do better?

Background: Cognitive impairment is common in Parkinson's disease (PD) and has a substantial impact on quality of life. Despite numerous trials targeting various PD features, we still lack effective treatments for cognition beyond cholinesterase inhibitors. Objective: To identify the gaps in recent clinical trials with cognitive outcomes in PD and consider areas for improvement. Methods: We examined recent clinical trials with cognitive outcomes in PD registered on ClinicalTrials.gov, excluding trials without cognitive outcomes, non-interventional studies, and in atypical Parkinsonian disorders. Included trials were categorized by treatment approach (investigational medicinal product, behavioral, physical activity, device-based). Details of trial design and outcomes were collected. Results: 178 trials at different stages of trial completion were considered. 46 trials were completed, 25 had available results. Mean follow-up duration was 29.9 weeks. Most common cognitive measure was Montreal Cognitive Assessment. Most were performed in North America or Europe. Majority of the participants identified as non-Hispanic and White. Only eight trials showed improvement in cognition, none showed improvement beyond four months. These included trials of international medicinal products, cognitive and physical interventions and devices. GRADE certainty levels ranged from Moderate to Very Low. Only mevidalen had a Moderate certainty for potential clinical effectiveness. Conclusions: Amongst a large number of trials for cognition in PD, only a small proportion were completed. Few showed significant improvement, with no proven long-lasting effects. Trial design, lack of enrichment for at-risk groups, short follow-up duration, insensitive outcome measures likely contribute to lack of detectable benefit and should be considered in future trials

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture

peer reviewedThe genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of dementia, and to generate a resource for the scientific community. Genome-wide association analysis identified five independent risk loci, whereas genome-wide gene-aggregation tests implicated mutations in the gene GBA. Genetic risk scores demonstrate that LBD shares risk profiles and pathways with Alzheimer’s disease and Parkinson’s disease, providing a deeper molecular understanding of the complex genetic architecture of this age-related neurodegenerative condition