NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations.

Genome-wide genotyping platforms have the capacity to capture genetic variation across different populations, but there have been disparities in the representation of population-dependent genetic diversity. The motivation for pursuing this endeavor was to create a comprehensive genome-wide array capable of encompassing a wide range of neuro-specific content for the Global Parkinson's Genetics Program (GP2) and the Center for Alzheimer's and Related Dementias (CARD). CARD aims to increase diversity in genetic studies, using this array as a tool to foster inclusivity. GP2 is the first supported resource project of the Aligning Science Across Parkinson's (ASAP) initiative that aims to support a collaborative global effort aimed at significantly accelerating the discovery of genetic factors contributing to Parkinson's disease and atypical parkinsonism by generating genome-wide data for over 200,000 individuals in a multi-ancestry context. Here, we present the Illumina NeuroBooster array (NBA), a novel, high-throughput and cost-effective custom-designed content platform to screen for genetic variation in neurological disorders across diverse populations. The NBA contains a backbone of 1,914,934 variants (Infinium Global Diversity Array) complemented with custom content of 95,273 variants implicated in over 70 neurological conditions or traits with potential neurological complications. Furthermore, the platform includes over 10,000 tagging variants to facilitate imputation and analyses of neurodegenerative disease-related GWAS loci across diverse populations. The NBA can identify low frequency variants and accurately impute over 15 million common variants from the latest release of the TOPMed Imputation Server as of August 2023 (reference of over 300 million variants and 90,000 participants). We envisage this valuable tool will standardize genetic studies in neurological disorders across different ancestral groups, allowing researchers to perform genetic research inclusively and at a global scale.

Open science takes on Parkinson's disease.

The Aligning Science Across Parkinson's (ASAP) initiative was set up to improve understanding of the biology underlying the onset and progression of Parkinson's disease. With an emphasis on open science and collaboration, we have assembled a research network led by nearly 100 investigators to explore the pathology of Parkinson's disease, and this network will soon expand to include researchers working on relevant (dys)-functional neural circuits. We have also contributed to large-scale genetics and patient cohort initiatives related to the disease. We hope that these actions, and others planned for the future, will deepen our knowledge of the molecular mechanisms underlying the origin and evolution of Parkinson's disease and, ultimately, contribute to the development of novel therapies.

Coordinating a new approach to basic research into Parkinson's disease.

The Aligning Science Across Parkinson's (ASAP) initiative is building an international network of researchers to improve our understanding of the biology underlying Parkinson's disease. Developing a better understanding of how the disease originates and progresses will, we hope, lead to new therapies. The ASAP initiative will incentivize collaboration between the existing PD research community and other researchers and will be committed to open-science practices.

Analysis of tauopathy research funding between 2006 and 2016 reveals critical gaps in research priorities.

Neurodegenerative diseases encompass a range of diagnoses, such as Alzheimer's disease and Parkinson's disease. Despite decades of advancements in understanding the neurobiology of individual diseases, this class has few disease-modifying therapeutics and a paucity of biomarkers for diagnosis or progression. However, tau protein aggregation has emerged as a potential unifying factor across several neurodegenerative diseases, which has prompted a rapid growth in tau-related funding. In spite of this growth, research funding in this area is not in line with the immense magnitude of disease burden, and drug discovery and clinical research remain underfunded. Coordinated, collaborative efforts are key to making an impact, which can and should be led by the major funding bodies within the tau space. Here we describe the development and analysis of a tau-focused neurodegeneration funding database, which captures data from 2040 grants from 2006 to 2016. This database was developed as a public resource to allow funders, researchers, and policy makers to better understand tau funding patterns and to identify key funders and potential collaborations. This database can be used in conjunction with other neurodegenerative disease databases, such as the International Alzheimer's Disease Research Portfolio to gain specific insight into tau-research funding. Over the study period, overall tau funding rose dramatically; however, changes in capital distribution also changed. Specifically, the field experienced a strong bias toward funding tau in the context of Alzheimer's disease, while at the same time generally decreasing the overall proportion of funding for basic research, treatment development, and evaluation. As funding organizations look forward, this resource can both inform future funding strategies and priority areas and identify potential collaborative efforts with complementary funding organizations.

Opportunities for epilepsy: Outcomes of the Milken Institute State of the Science Retreat.

The Milken Institute Center for Strategic Philanthropy has launched a Giving Smarter Program in Epilepsy to inform philanthropists on the state of the science for the epilepsy field, key challenges, and solutions to address them. As part of the program, the Milken Institute Center for Strategic Philanthropy hosted a retreat to identify strategic investments that would accelerate epilepsy research to ultimately improve care. The top three prioritized opportunities from the retreat were to 1) invest in data standards and analytical tool development, 2) support young investigators, and 3) promote cross-sector collaborations especially between basic scientists, preclinical researchers, clinicians, and patients.