Journal Article

DZNE-2025-01196

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases.

Feringa, F. M. ; Koppes-den Hertog, S. J. ; Wang, L. Y. ; Derks, R. J. E. ; Kruijff, I. ; Erlebach, L.DZNE* ; Heijneman, J. ; Miramontes, R. ; Pömpner, N. ; Blomberg, N. ; Olivier-Jimenez, D. ; Johansen, L. E. ; Cammack, A. J. ; Giblin, A. ; Toomey, C. E. ; Rose, I. V. L. ; Yuan, H. ; Ward, M. E. ; Isaacs, A. M. ; Kampmann, M. ; Kronenberg-Versteeg, D.DZNE* ; Lashley, T. ; Thompson, L. M. ; Ori, A. ; Mohammed, Y. ; Giera, M. ; van der Kant, R.

2025
Springer Nature [London]

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Please use a persistent id in citations: doi:10.1038/s42255-025-01365-z

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.

Keyword(s): Humans (MeSH) ; Lipidomics: methods (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Animals (MeSH) ; Mice (MeSH) ; Astrocytes: metabolism (MeSH) ; Lipid Metabolism (MeSH) ; Induced Pluripotent Stem Cells: metabolism (MeSH) ; Brain: metabolism (MeSH) ; Neurons: metabolism (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Microglia: metabolism (MeSH)

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Contributing Institute(s):

1. Glial Cell Biology (AG Kronenberg-Versteeg)
2. Cell Biology of Neurological Diseases (AG Jucker)

Research Program(s):

1. 351 - Brain Function (POF4-351) (POF4-351)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2025

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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