The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases

Femke M. Feringa; Sascha J. Koppes-den Hertog; Lian Y. Wang; Rico J.E. Derks; Iris Kruijff; Lena Erlebach; Jorin Heijneman; Ricardo Miramontes; Nadine Pömpner; Niek Blomberg; Damien Olivier-Jimenez; Lill Eva Johansen; Alexander J. Cammack; Ashling Giblin; Christina E. Toomey; Indigo V.L. Rose; Hebao Yuan; Michael E. Ward; Adrian M. Isaacs; Martin Kampmann; Deborah Kronenberg-Versteeg; Tammaryn Lashley; Leslie M. Thompson; Alessandro Ori; Yassene Mohammed; Martin Giera; Rik van der Kant

doi:10.1038/s42255-025-01365-z

The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases

Femke M. Feringa
, Sascha J. Koppes-den Hertog
, Lian Y. Wang
, Rico J.E. Derks
, Iris Kruijff
, Lena Erlebach
, Jorin Heijneman
, Ricardo Miramontes
, Nadine Pömpner
, Niek Blomberg
, Damien Olivier-Jimenez
, Lill Eva Johansen
, Alexander J. Cammack
, Ashling Giblin
, Christina E. Toomey
, Indigo V.L. Rose
, Hebao Yuan
, Michael E. Ward
, Adrian M. Isaacs
, Martin Kampmann

Deborah Kronenberg-Versteeg, Tammaryn Lashley, Leslie M. Thompson, Alessandro Ori, Yassene Mohammed, Martin Giera^*, Rik van der Kant^*

^*Corresponding author for this work

Research output: Contribution to Journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	2142-2164
Number of pages	43
Journal	Nature Metabolism
Volume	7
Issue number	10
Early online date	22 Sept 2025
DOIs	https://doi.org/10.1038/s42255-025-01365-z
Publication status	Published - Oct 2025

Bibliographical note

Publisher Copyright:
© The Author(s) 2025.

Funding

Funders	Funder number
Live Like Lou Foundation
Alzheimer’s Research UK
Fritz Lipmann Institute
Medical Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
UK Dementia Research Institute
National Institute of Neurological Disorders and Stroke
Organization postdoctoral fellowship
Studienstiftung des Deutschen Volkes
European Molecular Biology Laboratory
Leibniz-Gemeinschaft
VU University Medical Center
PhD Scholarship
Alzheimer's Association	ADSF-21-831212-C, 2019-AARG-643165, WE-03-2017-09P, 09150172110086
ZonMw	733050515, WE.03-2019-13
International Max Planck Research School for Environmental, Cellular and Molecular Microbiology	WE.15-2019-16
National Institute on Aging	U01 AG072464, R01 AG062359
Chan Zuckerberg Initiative	2020-221617, 2022-250474, 2022-250618, 2021-230967
California Institute for Regenerative Medicine	T32NS115706, EDUC412812, ADSF-21-816750
Genomics Research and Technology Hub Shared Resource	P30CA62203
National Institutes of Health	R35 NS116872, P01 NS084974-06A1
Gemeinnützige Hertie-Stiftung	P1230003
ZonMW Enabling Technologies Hotels	435005033

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Feringa, F. M., Koppes-den Hertog, S. J., Wang, L. Y., Derks, R. J. E., Kruijff, I., Erlebach, L., 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., ... van der Kant, R. (2025). The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases. Nature Metabolism, 7(10), 2142-2164. https://doi.org/10.1038/s42255-025-01365-z

@article{558a46bbca8341faab24b0927a2f9138,

title = "The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases",

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.",

author = "Feringa, \{Femke M.\} and \{Koppes-den Hertog\}, \{Sascha J.\} and Wang, \{Lian Y.\} and Derks, \{Rico J.E.\} and Iris Kruijff and Lena Erlebach and Jorin Heijneman and Ricardo Miramontes and Nadine P{\"o}mpner and Niek Blomberg and Damien Olivier-Jimenez and Johansen, \{Lill Eva\} and Cammack, \{Alexander J.\} and Ashling Giblin and Toomey, \{Christina E.\} and Rose, \{Indigo V.L.\} and Hebao Yuan and Ward, \{Michael E.\} and Isaacs, \{Adrian M.\} and Martin Kampmann and Deborah Kronenberg-Versteeg and Tammaryn Lashley and Thompson, \{Leslie M.\} and Alessandro Ori and Yassene Mohammed and Martin Giera and \{van der Kant\}, Rik",

note = "Publisher Copyright: {\textcopyright} The Author(s) 2025.",

year = "2025",

month = oct,

doi = "10.1038/s42255-025-01365-z",

language = "English",

volume = "7",

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Feringa, FM, Koppes-den Hertog, SJ, Wang, LY, Derks, RJE, Kruijff, I, Erlebach, L, Heijneman, J, Miramontes, R, Pömpner, N, Blomberg, N, Olivier-Jimenez, D, Johansen, LE, Cammack, AJ, Giblin, A, Toomey, CE, Rose, IVL, Yuan, H, Ward, ME, Isaacs, AM, Kampmann, M, Kronenberg-Versteeg, D, Lashley, T, Thompson, LM, Ori, A, Mohammed, Y, Giera, M & van der Kant, R 2025, 'The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases', Nature Metabolism, vol. 7, no. 10, pp. 2142-2164. https://doi.org/10.1038/s42255-025-01365-z

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T1 - The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases

AU - Feringa, Femke M.

AU - Koppes-den Hertog, Sascha J.

AU - Wang, Lian Y.

AU - Derks, Rico J.E.

AU - Kruijff, Iris

AU - Erlebach, Lena

AU - Heijneman, Jorin

AU - Miramontes, Ricardo

AU - Pömpner, Nadine

AU - Blomberg, Niek

AU - Olivier-Jimenez, Damien

AU - Johansen, Lill Eva

AU - Cammack, Alexander J.

AU - Giblin, Ashling

AU - Toomey, Christina E.

AU - Rose, Indigo V.L.

AU - Yuan, Hebao

AU - Ward, Michael E.

AU - Isaacs, Adrian M.

AU - Kampmann, Martin

AU - Kronenberg-Versteeg, Deborah

AU - Lashley, Tammaryn

AU - Thompson, Leslie M.

AU - Ori, Alessandro

AU - Mohammed, Yassene

AU - Giera, Martin

AU - van der Kant, Rik

PY - 2025/10

Y1 - 2025/10

N2 - 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.

AB - 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.

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DO - 10.1038/s42255-025-01365-z

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EP - 2164

JO - Nature Metabolism

JF - Nature Metabolism

IS - 10

ER -

The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases

Abstract

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