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PXD066703-1

PXD066703 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThe Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4
DescriptionLipid changes in the brain have been implicated in many neurodegenerative diseases including Alzheimers Disease (AD), Parkinsons disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named the Neurolipid Atlas, that we have pre-populated with novel human, mouse and isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. We show that iPSC-derived neurons, microglia and astrocytes display distinct lipid profiles that recapitulate in vivo lipotypes. Leveraging multiple datasets, we show that the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation in human astrocytes recapitulating CE accumulation measured in the human AD brain. Multi-omic interrogation of iPSC-derived astrocytes revealed that cholesterol plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex (MHC) class I antigen presentation. We show that through enhanced cholesterol esterification ApoE4 suppresses immune activation of astrocytes. Our novel data commons, available at neurolipidatlas.com, provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.
HostingRepositoryMassIVE
AnnounceDate2025-07-29
AnnouncementXMLSubmission_2025-07-29_01:54:47.918.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLeibniz FLI Proteomics
SpeciesList scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationListCarbamidomethyl; Acetyl; Oxidation
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-07-29 00:22:36ID requested
12025-07-29 01:54:48announced
Publication List
no publication
Keyword List
submitter keyword: ApoE4, neurolipids, Alzheimer Disease (AD), Parkinson disease, Amyotrophic Lateral Sclerosis, DatasetType:Proteomics
Contact List
Rik van der Kant
contact affiliationCenter for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam,
contact emailr.h.n.vander.kant@vu.nl
lab head
Leibniz FLI Proteomics
contact affiliationLeibniz FLI
contact emailproteomics@leibniz-fli.de
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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