PXD052263
PXD052263 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | The influence of APOE4 on the pTau interactome in sporadic Alzheimers disease |
| Description | APOE4 is the major genetic risk factor for sporadic Alzheimers disease (AD). Although APOE4 is well known to promote Abeta pathology, recent data also support an effect of APOE polymorphism on phosphorylated Tau (pTau) pathology. To elucidate these potential effects, the pTau interactome was analyzed across APOE genotypes in the frontal cortex of 10 advanced AD cases (n=5 APOE3 and n=5 APOE4), using a combination of anti-pTau PHF1 (pS396/pS404) immunoprecipitation and mass spectrometry. This proteomic approach was complemented by a neuropathological analysis of anti-pTau PHF1 and anti-Abeta 4G8 immunohistochemistry, performed in the frontal cortex of 21 advanced AD cases (n=11 APOE3 and n=10 APOE4). Our dataset includes 1130 and 1330 proteins enriched in IPPHF1 samples from APOE3 and APOE4 groups (FC over 1.50, IPPHF1 versus IPIgG ctrl). We identified 80 and 68 proteins as strong pTau interactors in APOE3 and APOE4 groups, respectively (SAINT score above 0.80; FDR under 5%). A total of 47/80 proteins were identified as strong pTau interactors only for APOE3 cases. Functional enrichment analyses showed that they were significantly associated with the nucleoplasm compartment and involved in RNA processing. In contrast, 35/68 proteins were identified as strong pTau interactors only for APOE4 cases. They were significantly associated with the synaptic compartment and involved in cellular transport. A comprehensive characterization of Tau pathology in the frontal cortex showed a higher density of plaque-associated neuritic crowns, made of dystrophic axons and synapses, in APOE4 carriers. Cerebral amyloid angiopathy was more frequent and severe in APOE4 cases. Our study supports an influence of APOE genotype on pTau subcellular location in the human brain. These results are consistent with a facilitation of pTau progression to Abeta-affected brain regions of APOE4 carriers, paving the way to the identification of potential new therapeutic targets. This entry contains the mass spectrometric raw files for the immune purifications. |
| HostingRepository | MassIVE |
| AnnounceDate | 2024-05-15 |
| AnnouncementXML | Submission_2024-05-15_06:39:04.446.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Beatrix Ueberheide |
| SpeciesList | scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; |
| ModificationList | Oxidation; Deamidated |
| Instrument | Orbitrap Eclipse |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2024-05-14 15:00:12 | ID requested | |
| ⏵ 1 | 2024-05-15 06:39:04 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Alzheimer's Disease, phosphorylated Tau, ApoE genotype, immuno purification |
Contact List
| Beatrix Ueberheide | |
|---|---|
| contact affiliation | NYU School of Medicine |
| contact email | beatrix.ueberheide@nyulangone.org |
| lab head | |
| Beatrix Ueberheide | |
| contact affiliation | NYU School of Medicine |
| contact email | beatrixueberheide@gmail.com |
| 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.ucsd.edu/v07/MSV000094757/ |
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