⮝ Full datasets listing
PXD065278
PXD065278 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | EIF4A1-Dependent Translation Mediates APOE2-Driven Synaptic Regulation and Attenuates Alzheimer's Disease-Associated Pathways in Human Neurons |
| Description | Apolipoprotein E4 (APOE4) is the greatest genetic risk factor for late-onset Alzheimer's disease (AD), but APOE2 is associated with exceptional longevity and healthspan. To investigate APOE2's protective mechanisms, we generated isogenic APOE2/2, APOE3/3, and APOE4/4 induced pluripotent stem cells (iPSCs) and differentiated them into glutamatergic neurons. The neuronal network of APOE2 neurons exhibited lower burst frequency and greater synchrony than APOE4 neurons. APOE4 neurons displayed an aberrant increased synaptic density compared to APOE2 and APOE3 neurons. Proteomic analysis identified eukaryotic translation initiation factor 4A1 (EIF4A1), as the key protein driving the separate proteomic clustering of the three APOE protein isoforms. EIF4A1 levels were higher in APOE2 iPSC-derived neurons, human postmortem brain from APOE2 carriers, and human APOE2-targeted replacement mice. We propose that EIF4A1 is essential for proper synaptic homeostasis mediated by APOE2. EIF4A1 expression rescued the aberrant synaptic density in APOE4 neurons by enhancing C-terminal binding protein (CTBP1) translation, a transcriptional corepressor that restricts synaptogenesis. Polysome profiling of APOE4 neurons overexpressing EIF4A1 revealed a selective translation shift away from mRNAs involved in amyloid fibril formation, mitochondrial dysfunction, and endosomal transport. These processes are dysregulated in AD. Our findings suggest that APOE2 mediates its neuroprotective effects by upregulating EIF4A1. |
| HostingRepository | MassIVE |
| AnnounceDate | 2026-08-12 |
| AnnouncementXML | Submission_2026-08-12_11:16:46.667.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 | 2025-06-20 13:56:25 | ID requested | |
| ⏵ 1 | 2026-08-12 11:16:47 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Data-independent acquisition (DIA), Apolipoprotein E, iPSC-derived neurons, Eukaryotic translation initiation factor 4A1 (EIF4A1), 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/MSV000098276/ |
