⮝ Full datasets listing
PXD064885
PXD064885 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The Longevity Gene APOE2 Enhances Pericyte Function and Reduces Lipid Droplets |
| Description | Pericytes are critical for maintaining blood-brain barrier (BBB) integrity and have emerged as key contributors to Alzheimer's disease (AD) pathogenesis. Although the Apolipoprotein E2 (APOE2) allele is associated with reduced AD risk and increased longevity, its impact on pericyte function remains largely unexplored. To address this, we assessed pericyte density in the brains of human APOE2, APOE3, and APOE4 knock-in mice and found that APOE2 mice exhibit increased pericyte marker and improved BBB integrity. To uncover the underlying mechanisms, we generated isogenic human iPSC-derived pericytes carrying APOE2, APOE3, or APOE4 alleles using CRISPR/Cas9 editing. All lines expressed pericyte markers in an APOE-dependent manner. Using a human in vitro BBB model incorporating endothelial cells, astrocytes, and genotype-specific pericytes, we found that APOE2 pericytes conferred significantly greater barrier integrity. APOE2 pericytes also showed enhanced resistance to senescence and reduced amyloid-beta levels. Unbiased proteomic profiling subsequently revealed significant alterations in lipid metabolism-related proteins. Untargeted lipidomic analysis confirmed a genotype-specific lipid signature and revealed a reduction in phospholipids and an increase in triglycerides in APOE2 pericytes. Interestingly, APOE2 pericytes showed lower lipid droplets (LDs) accumulation. Further analysis revealed increased expression of proteins involved in lipid degradation, beta-oxidation, and lipid transport, suggesting more efficient lipid processing. Notably, treatment with recombinant APOE2 protein rescued pericyte function and mitigated LDs accumulation in APOE3 and APOE4 pericytes. In conclusion, these findings demonstrate that APOE2 enhances pericyte functionality through increased lipid processing, providing mechanistic insight into the protective effects of APOE2 in pericytes and underscore the molecular pathways involved. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-08-11 |
| AnnouncementXML | Submission_2026-08-11_14:53:19.113.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Joanna Bons |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-06-11 09:49:22 | ID requested | |
| ⏵ 1 | 2026-08-11 14:53:19 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Data-independent acquisition (DIA), Apolipoprotein E, Alzheimer's disease, Blood-brain barrier, Senescence, Quantitative proteomics, DatasetType:Proteomics |
Contact List
| Birgit Schilling | |
|---|---|
| contact affiliation | Buck Institute |
| contact email | bschilling@buckinstitute.org |
| lab head | |
| Joanna Bons | |
| contact affiliation | Buck Institute for Research on Aging |
| contact email | jbons@buckinstitute.org |
| dataset submitter | |
Full Dataset Link List
| MassIVE dataset URI |
| Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://massive-ftp.ucsd.edu/v10/MSV000098122/ |
