Welcome to the third edition of the Aligning Science Across Parkinson’s (ASAP) Research Round-Up. In this issue, we highlight advancements from the past quarter across the ASAP portfolio that funnel new ideas into Parkinson’s disease (PD) research, facilitate the exchange of scientific ideas, expand access to resources for PD research, and support the next generation of Parkinson’s disease researchers.
In the third quarter of 2025, ASAP advanced insights into neural circuits disrupted in Parkinson’s and contributed to our understanding of the biology underlying PD-related alterations to lipid metabolism, autophagy, synaptic function, and more.
Insights into the neural circuits controlling movement
Progressive loss of dopamine neurons in the substantia nigra pars compacta (SNc) and their projection to the dorsal striatum are associated with motor symptoms of PD. However, it is increasingly apparent that PD pathology extends beyond the SNc and the specific mechanisms underlying pathology across the brain remain poorly understood. Recent papers from the ASAP initiative have contributed to a growing body of research uncovering how PD disrupts the precise neural circuits that control movement. Some are listed below:
- Postsynaptic adaptation in direct pathway muscarinic M4 receptor signaling displays regional and temporal patterns in PD (Team Edwards)
- The timing of globus pallidus neuronal activity becomes uncoupled from movement onset in PD (Team Strick)
- Primary motor cortex neuron subpopulation (PT5B) drives enhanced beta power oscillations in PD (Team Strick)
Insights into mechanisms of lipid regulation
Genetic studies of PD have identified mutations in genes such as GBA1 and ATP10B, which can disrupt lipid regulation. However, the consequences of these mutations on PD pathology remain unclear. Recent ASAP-funded studies have revealed the essential roles of lipids in neuronal health and in cellular quality-control pathways. Some are listed below:
- Loss of lysosomal lipid flippase ATP10B leads to progressive dopaminergic neurodegeneration and motor deficits (Team Vangheluwe)
- Lipid transport proteins VPS13A, VPS13C, and ATG9A are important for autophagosome biogenesis and membrane integrity (Team De Camilli and Hurley)
- Lipid metabolism at neuronal synapses is regulated by a neuron-specific DDHD2 lipase (Team De Camilli)
Insights into LRRK2-mediated disruptions to neuronal and immune function
Activating mutations in the LRRK2 gene are among the most common monogenic causes of PD and represent one of the strongest risk factors for sporadic PD. Understanding the mechanisms by which LRRK2 mutations contribute to disease progression is critical for developing new treatments. Recent papers from the ASAP initiative have revealed roles for LRRK2 in neuronal signaling, iron metabolism, and immune regulation. Some are listed below:
- Iron homeostasis is disrupted in neurons with PD-associated LRRK2 mutations (Team Desjardins)
- Cilia formation is impaired in striatal neurons and astrocytes with PD-associated LRRK2 mutations (Team Alessi)
- PD-associated LRRK2 mutations drive immune cell dysregulation in the gut (Team Desjardins)
- Secretion of extracellular vesicles is upregulated in neurons with PD-associated LRRK2 mutations (Team Hurley)
Driving new research
ASAP co-funded the Immune Consortium with The Michael J. Fox Foundation to establish frameworks and centralized infrastructure for future neuroimmune biomarker discovery in PD. Recently, the Immune Consortium issued a Request for Information (RFI) to identify cohorts that include individuals with PD across the disease spectrum and have existing immune data or relevant biosamples available for analysis. The RFI closed on September 17, receiving more than 35 responses from cohorts worldwide.
In the third quarter of 2025, ASAP supported in-person and virtual workshops and webinars to accelerate the exchange of scientific knowledge.
- LRRK2 Central and mito911 hosted webinars with speakers from seven different institutions across five countries.
Interested in joining these webinars? You can learn more about upcoming events and register to attend on the ASAP website. Check it out!
- GP2 held its Africa Investigators Meeting in Ghana, bringing together 18 investigators from nine countries. Discussions focused on progress in PD research in Africa, capacity building, sustainability, and patient engagement, underscoring the vital role of African investigators in advancing PD science.
- BLAAC PD convened its annual meeting in August, where investigators and coordinators discussed recruitment progress and genetic analyses. A key topic was identifying where Black and African American individuals living with PD receive care.
Promoting Open Science
Promoting open science is at the core of ASAP’s mission. In the third quarter of 2025, ASAP engaged with the broader open science community and contributed to ongoing policy discussions, including:
- Endorsing the Preprints Policy Framework from ASAPbio and Creative Commons, which provides a model for funder and research organizations to align around six key components to promote open science practices.
- Presenting at the International Congress of Peer Review and Scientific Publication about funder-led interventions to increase sharing of data, code, protocols, and key lab materials
Robert Thibault, PhD, open science team member with ASAP, speaks at the International Congress of Peer Review and Scientific Publication
- Responding to the NIH Response for Information on limiting allowable publication costs to maximize research funds.
Interested in learning more? Read ASAP’s response to the NIH RFI.
ASAP also continues to ensure that datasets generated through its funding are publicly available to the research community. In the third quarter of 2025, this included:
- The 3rd CRN Cloud data release expanded the human postmortem-derived brain sequencing collection to include spatial transcriptomics and introduced new non-human (mouse) datasets.
- A collaboration between the CRN Cloud and Allen Institute added data from patients with PD to the ABC Atlas, increasing the dataset by nearly 50%, marking the first inclusion of PD patient data in the Atlas.
Prajal Bishwakarma, a scientific data engineer at the Allen Institute, analyzes new Parkinson’s data from ASAP, which is now available in the Allen Institute’s Allen Brain Cell Atlas.
Interested in the ABC Atlas? Explore data from Parkinson’s and Alzheimer’s patients!
- The 10th GP2 data release significantly expanded available genomic and clinical data, now including over 83,000 genotyped samples.
- GP2 published an article highlighting its transformative, global approach to PD research.
Interested in GP2? You can read the latest news and blogs. Check out this video about GP2 data releases!
Building Tools and Resources for the PD Research Community
ASAP-funded programs continue to generate outputs, tools, and resources that bring the research community and patients closer to understanding Parkinson’s disease:
- AutoMorphoTrack: a software package for analyzing organelle morphology, motility, and colocalization (Team Chen)
- GEM-SCOPe: a toolkit for visualizing lysosomal and mitochondrial dysfunction (Team Vangheluwe)
- A protocol for CRISPR-based manipulation and visualization of endogenous α-synuclein (Team Gradinaru)
The Discover ASAP video series also spotlighted three resources from the ASAP community:
- A Fluid-Walled Microfluidic Platform to Study Human Microcircuitry (Team Cragg)
- NeuroBooster Array: A Genome-Wide Genotyping Platform to Study Neurological Disorders Across Diverse Populations (Team GP2)
- EndoMAP: An Interactive Data Visualization Tool of the Endosomal Structural Interactome (Team Harper)
Interested in viewing past Discover ASAP videos? ASAP created a YouTube playlist containing recordings of these interviews. Check it out!
In the third quarter of 2025, ASAP supported opportunities for emerging professionals through:
- A GP2 Hackathon in Germany, bringing trainees together for hands-on learning, collaboration, and mentorship. Projects included developing a LRRK2 Browsing Tool, evaluating polygenic risk scores using GP2’s recent European meta-GWAS summary statistics, exploring cell-type-specific genetic enrichment, and identifying genome-wide repeat expansions.
- Bioinformatics workshops for GP2 trainees in Chile, Ghana, and Mexico, offering hands-on training using GP2 and LARGE-PD datasets to analyze polygenic risk scores.
- Continuing the 2025 Care & Career Program, which provides up to $10,000 per eligible household to offset family-care costs (applications closed September 30).
- Launching the CRN Discovery Fellowship, a nomination-based program for exceptional postdoctoral fellows within ASAP’s CRN, designed to encourage bold, trainee-led projects and foster independence (applications closed September 16).
Thank you for reading this edition of the ASAP Research Round-Up. We look forward to sharing continued progress in research, collaboration, and resource development that advance our understanding of Parkinson’s disease. Looking ahead, ASAP remains committed to fostering innovation, inclusivity, and collaboration across the global PD research community. For more updates on upcoming events, publications, and key developments, visit our ASAP Highlights page.
