⮝ Full datasets listing
PXD068037
PXD068037 is an original dataset announced via ProteomeXchange.
Dataset Summary
| Title | Human Apolipoprotein E4 Drives Female Disrupted Osteocyte Function and Bone Fragility |
| Description | Individuals diagnosed with Alzheimers Disease - AD are at an increased risk of bone fracture. Conversely, a diagnosis of osteoporosis in females is the earliest known predictor for AD. However, mechanisms responsible for the coupled decline in cognitive and skeletal health remain unclear. In proteomic analysis of aged mouse cortical bone, we unexpectedly find several neurological disease-associated factors, including apolipoprotein E , amyloid precursor protein, and others, in the 10 percent most abundant proteins. APOE localizes specifically to bone-embedded osteocytes, with expression in aged female bone exceeding that in young or male counterparts. In humans, APOE allele variants carry differing AD risk with age. To investigate their role in bone, we used a humanized APOE knock-in mouse model that expresses the protective APOE2, neutral APOE3, or AD risk factor APOE4 alleles. APOE4 exerts strong sex-specific effects on the bone transcriptome and proteome, relative to APO2 or APOE3. APOE4-dependent disruption of the female bone proteome is an order of magnitude more severe than in hippocampus of the same mice. The APOE4 allele causes bone fragility in females, but not males, prior to age-related losses to bone mass or cognition. This bone quality deficit arises from deregulation of osteocyte function and suppression of perilacunocanalicular remodeling. Our finding suggest that osteocyte-driven regulation of bone quality is an early and under appreciated target of APOE4, preceding cognitive decline and disproportionately affecting females. Thus, bone may provide new strategies to understand and intervene in age-related cognitive decline. |
| HostingRepository | MassIVE |
| AnnounceDate | 2025-12-22 |
| AnnouncementXML | Submission_2025-12-22_11:50:12.393.xml |
| DigitalObjectIdentifier | |
| ReviewLevel | Non peer-reviewed dataset |
| DatasetOrigin | Original dataset |
| RepositorySupport | Unsupported dataset by repository |
| PrimarySubmitter | Charles Schurman |
| SpeciesList | scientific name: Mus musculus; common name: house mouse; NCBI TaxID: 10090; |
| ModificationList | No PTMs are included in the dataset |
| Instrument | Orbitrap Exploris 480 |
Dataset History
| Revision | Datetime | Status | ChangeLog Entry |
|---|---|---|---|
| 0 | 2025-09-03 13:31:10 | ID requested | |
| ⏵ 1 | 2025-12-22 11:50:12 | announced |
Publication List
| no publication |
Keyword List
| submitter keyword: Bone, Osteocytes, Alzheimer's Disease, Apoplipoprotein E, DatasetType:Proteomics |
Contact List
| Birgit Schilling | |
|---|---|
| contact affiliation | Buck Institute |
| contact email | bschilling@buckinstitute.org |
| lab head | |
| Charles Schurman | |
| contact affiliation | Buck Institute for research On Aging |
| contact email | cschurman@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/MSV000099018/ |
