New Platform Uses Patient Olfactory Neurons to Study Neurodegenerative Disease
Scientists have developed a platform called Gateway that uses guided biopsies of olfactory neurons from living patients to generate large-scale single-cell transcriptomic data, producing an atlas of 4 million cells from 202 donors. Olfactory sensory neurons are accessible without brain surgery and share developmental and transcriptional links to the central nervous system, making them a practical proxy for studying brain disease. The work could accelerate target discovery and biomarker development for Alzheimer's and Parkinson's disease without requiring invasive brain sampling.
Gateway is a newly described research platform that combines device-guided olfactory epithelium biopsy, onsite tissue fixation, and 10x Genomics FLEX RNA profiling to capture single-cell gene expression data from neurons in living patients. The resulting atlas encompasses approximately 4 million cells drawn from 202 human donors, including healthy controls and individuals diagnosed with neurodegenerative diseases, and has been released publicly through the CELLxGENE platform. Researchers report that olfactory neurons express more brain-enriched genes than other clinically accessible tissue types, such as blood or cerebrospinal fluid, strengthening their value as a CNS proxy. In exploratory analyses of Alzheimer's and Parkinson's disease, the team identified dysregulation of pathways and genome-wide association study (GWAS)-implicated genes tied to neuroinflammation, endolysosomal biology, proteostasis, and synaptic maintenance. The study addresses a longstanding bottleneck in dementia research: the living human brain cannot be routinely biopsied during disease progression, limiting molecular insight into how these diseases develop. With an estimated 42% of Americans over 55 projected to develop dementia, scalable, minimally invasive approaches to studying patient neurons carry significant clinical and therapeutic implications. The authors position Gateway as a complementary modality alongside existing tools rather than a replacement for post-mortem or imaging-based studies.
What's missing
As a preprint on bioRxiv, this work has not yet undergone formal peer review, and the reproducibility of the biopsy procedure across different clinical sites and operators has not been independently validated. The exploratory nature of the Alzheimer's and Parkinson's findings means causal relationships between identified gene dysregulation and disease mechanisms remain unestablished. The study does not report longitudinal data tracking the same patients over time, limiting conclusions about disease progression.
What different sources said
- bioRxivCenter
Gateway: patient olfactory neurons for large-scale discovery in neurodegenerative disease
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