The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases
Lipid alterations in the brain have been implicated in many neurodegenerative diseases. To facilitate comparative lipidomic research across brain diseases, we establish a data common named the Neurolipid Atlas that we prepopulated with isogenic induced pluripotent stem cell (iPS cell)-derived lipidomics data for different brain diseases. Additionally, the resource contains lipidomics data of human and mouse brain tissue. Leveraging multiple datasets, we demonstrate that iPS cell-derived neurons, microglia and astrocytes exhibit distinct lipid profiles that recapitulate in vivo lipotypes. Notably, the Alzheimer disease (AD) risk gene ApoE4 drives cholesterol ester (CE) accumulation specifically in human astrocytes and we also observe CE accumulation in whole-brain lipidomics from persons with AD. Multiomics interrogation of iPS cell-derived astrocytes revealed that altered cholesterol metabolism has a major role in astrocyte immune pathways such as the immunoproteasome and major histocompatibility complex class I antigen presentation. Our data commons, available online ( https://neurolipidatlas.com/ ), allows for data deposition by the community and provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.
Authors
- Rik van der Kant (ORCID: https://orcid.org/0000-0002-7023-0106)
- Indigo V.L. Rose (ORCID: https://orcid.org/0000-0003-0491-1269)
- Li-Chiao Wang (ORCID: https://orcid.org/0009-0006-0509-6680)
- Alexander J. Cammack (ORCID: https://orcid.org/0000-0002-9624-9067)
- Martin Giera (ORCID: https://orcid.org/0000-0003-1684-1894)
- Lill Eva Johansen (ORCID: https://orcid.org/0000-0003-2187-6709)
- Alessandro Ori (ORCID: https://orcid.org/0000-0002-3046-0871)
- Femke M. Feringa (ORCID: https://orcid.org/0000-0002-6003-4048)
- Leslie Michels Thompson (ORCID: https://orcid.org/0000-0003-4573-9514)
- Christina E. Toomey (ORCID: https://orcid.org/0000-0002-5146-3326)
- Lena Erlebach (ORCID: https://orcid.org/0000-0002-9077-8689)
- Sascha Koppes-den Hertog (ORCID: https://orcid.org/0000-0002-7372-8946)
- Damien Olivier‐Jimenez (ORCID: https://orcid.org/0000-0002-6363-0857)
- Ricardo Miramontes (ORCID: https://orcid.org/0000-0002-9231-2479)
- Tammaryn Lashley (ORCID: https://orcid.org/0000-0001-7389-0348)
- Hebao Yuan (ORCID: https://orcid.org/0000-0003-4425-3678)
- Nadine Pömpner
- Deborah Kronenberg‐Versteeg (ORCID: https://orcid.org/0000-0003-0965-9998)
- Rico J. E. Derks (ORCID: https://orcid.org/0000-0002-8920-7133)
- Adrian M. Isaacs (ORCID: https://orcid.org/0000-0002-6820-5534)
- Martin Kampmann (ORCID: https://orcid.org/0000-0002-3819-7019)
- Yassene Mohammed (ORCID: https://orcid.org/0000-0003-3265-3332)
- Jorin Heijneman
- Michael E. Ward
- Iris Kruijff
- Niek Blomberg
Institutions
- National Institutes of Health (US)
- University of California, San Francisco (US)
- University of California, Irvine (US)
- Leiden University Medical Center (NL)
- German Center for Neurodegenerative Diseases (DE)
- Netherlands Metabolomics Centre (NL)
- Amsterdam Neuroscience (NL)
- National Institute of Neurological Disorders and Stroke (US)
- Institute for Neurodegenerative Disorders (US)
- UK Dementia Research Institute (GB)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- MRC Unit for Lifelong Health and Ageing (GB)
- Hertie Institute for Clinical Brain Research (DE)
- National Hospital for Neurology and Neurosurgery (GB)
- Cognitive Research (United States) (US)
- University College London (GB)
- McGill University (CA)
- University of Tübingen (DE)
- Vrije Universiteit Amsterdam (NL)
Publication Details
- Journal
- Nature Metabolism
- Published
- 2025-09-22
- DOI
- https://doi.org/10.1038/s42255-025-01365-z
- Citations
- 11
- Primary Topic
- Cholesterol and Lipid Metabolism
- Type
- article
- Field-Weighted Citation Impact
- 22.07