TY - JOUR
T1 - The Neurolipid Atlas
T2 - 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
N1 - Publisher Copyright:
© The Author(s) 2025.
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.
UR - https://www.scopus.com/pages/publications/105017040585
U2 - 10.1038/s42255-025-01365-z
DO - 10.1038/s42255-025-01365-z
M3 - Article
C2 - 40983680
SN - 2522-5812
VL - 7
SP - 2142
EP - 2164
JO - Nature Metabolism
JF - Nature Metabolism
IS - 10
ER -