Population-scale cross-disorder atlas of the human prefrontal cortex at single-cell resolution
Neurodegenerative diseases and serious mental illnesses often exhibit overlapping characteristics, highlighting the potential for shared underlying mechanisms. To facilitate a deeper understanding of these diseases and pave the way for more effective treatments, we have generated a population-scale multi-omics dataset consisting of genotype and single-nucleus transcriptome data from the prefrontal cortex of frozen human brain specimens. Encompassing over 6.3 million nuclei from 1,494 donors, our dataset represents a diverse range of neurodegenerative and serious mental illnesses, including Alzheimer's and Parkinson's diseases, schizophrenia, bipolar disorder and diffuse Lewy body dementia, as well as neurotypical controls. Our dataset offers a unique opportunity to study disease interactions, as 21% of donors had comorbid diagnoses of two or more major brain disorders. Additionally, it includes detailed phenotypic information on neuropsychiatric symptoms, such as apathy and weight loss, which commonly accompany Alzheimer's disease and related dementias. We have performed stringent preprocessing and quality controls, ensuring the reliability and usability of the data. As a commitment to fostering collaborative research, we provide this valuable resource as an online repository, enabling widespread analyses across the scientific community.
Authors
- Sanan Venkatesh (ORCID: https://orcid.org/0000-0002-3094-2731)
- Pavan K. Auluck (ORCID: https://orcid.org/0000-0003-4799-7904)
- John F. Fullard (ORCID: https://orcid.org/0000-0001-9874-2907)
- Lisa L. Barnes (ORCID: https://orcid.org/0000-0002-0072-9817)
- Tereza Clarence (ORCID: https://orcid.org/0000-0002-0099-2797)
- Zhiping Shao (ORCID: https://orcid.org/0009-0006-4889-6637)
- Deepika Mathur (ORCID: https://orcid.org/0000-0002-2591-4170)
- Marcela Alvia (ORCID: https://orcid.org/0000-0001-9706-1376)
- Karen Therrien (ORCID: https://orcid.org/0000-0003-3351-7260)
- Clara Casey (ORCID: https://orcid.org/0009-0002-9430-3557)
- David Burstein (ORCID: https://orcid.org/0000-0003-0615-8178)
- Aram Hong (ORCID: https://orcid.org/0009-0000-6083-1998)
- Stathis Argyriou (ORCID: https://orcid.org/0009-0008-0713-6599)
- Stefano Marenco (ORCID: https://orcid.org/0000-0002-2488-2365)
- Donghoon Lee (ORCID: https://orcid.org/0000-0003-0453-6059)
- David A. Bennett
- Prashant Nm
Institutions
- University of Copenhagen (DK)
- Rush University Medical Center (US)
- Allen Institute for Brain Science (US)
- Gladstone Institutes (US)
- University of Wisconsin–Madison (US)
- University of Pittsburgh (US)
- University of California, San Francisco (US)
- Novo Nordisk Foundation (DK)
- Institute for Neurodegenerative Disorders (US)
- James J. Peters VA Medical Center (US)
- Translational Therapeutics (United States) (US)
- National Institute of Mental Health (US)
- Vanderbilt University Medical Center (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Scientific Data
- Published
- 2025-06-06
- DOI
- https://doi.org/10.1038/s41597-025-04687-5
- Citations
- 9
- Primary Topic
- Single-cell and spatial transcriptomics
- Type
- article
- Field-Weighted Citation Impact
- 5.64
Funders
- Georgia Clinical and Translational Science Alliance
- National Institutes of Health
- National Institute on Aging
- National Institute of Mental Health
- National Center for Advancing Translational Sciences