The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases PMID: 40983680

ADC Targets in Oncology

2026-04-10

The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases

Nat Metab. 2025 Oct;7(10):2142-2164. doi: 10.1038/s42255-025-01365-z.

Femke M Feringa ^# ¹ , Sascha J Koppes-den Hertog ^# ¹ ² , Lian Y Wang ³ , Rico J E Derks ³ , Iris Kruijff ¹ ² , Lena Erlebach ⁴ ⁵ , Jorin Heijneman ¹ ² , Ricardo Miramontes ⁶ ⁷ ⁸ , Nadine Pömpner ⁹ , Niek Blomberg ³ , Damien Olivier-Jimenez ³ , Lill Eva Johansen ¹ , Alexander J Cammack ¹⁰ ¹¹ , Ashling Giblin ¹¹ ¹² , Christina E Toomey ¹⁰ , Indigo V L Rose ¹³ ¹⁴ , Hebao Yuan ¹⁵ , Michael E Ward ¹⁵ , Adrian M Isaacs ¹⁰ ¹¹ , Martin Kampmann ¹³ ¹⁶ , Deborah Kronenberg-Versteeg ⁴ ⁵ , Tammaryn Lashley ¹⁰ , Leslie M Thompson ⁶ ⁷ ⁸ , Alessandro Ori ⁹ ¹⁷ , Yassene Mohammed ³ ¹⁸ , Martin Giera ¹⁹ , Rik van der Kant ²⁰ ²¹

Affiliations

1. Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands.
2. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands.
3. Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, The Netherlands.
4. German Center for Neurodegenerative Diseases (DZNE) Tübingen, Tübingen, Germany.
5. Department of Cellular Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
6. Department of Psychiatry and Human Behavior, University of California, Irvine, Irvine, CA, USA.
7. Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, USA.
8. Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, Irvine, CA, USA.
9. Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany.
10. Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.
11. UK Dementia Research Institute, University College London, London, UK.
12. Institute of Healthy Ageing, University College London, London, UK.
13. Institute for Neurodegenerative Diseases, University of California, San Francisco, San Francisco, CA, USA.
14. Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA, USA.
15. National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
16. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.
17. Genentech, Inc., San Francisco, CA, USA.
18. Gerald Bronfman Department of Oncology, McGill University, Montreal, Quebec, Canada.
19. Leiden University Medical Center, Center for Proteomics and Metabolomics, Leiden, The Netherlands. [email protected].
20. Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands. [email protected].
21. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam University Medical Center, Amsterdam Neuroscience, Amsterdam, The Netherlands. [email protected].
# Contributed equally.

Abstract

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.