iProXProteomicsZheng ZhaoMus Musculushttp://www.iprox.org/page/project.html?id=IPX0017756000zhaozheng201007@163.comAffiliated Kangning Hospital of Ningbo University (Ningbo Kangning Hospital)iProXfalseIntegrated Proteomic and Phosphoproteomic Profiling Reveals Distinct Disease- and Age-Related Molecular Alterations in the Retina and Hippocampus of APP/PS1/MAPT MiceBackground: Retinal abnormalities have emerged as promising noninvasive indicators of early Alzheimer’s disease (AD), yet the molecular relationship between retinal and hippocampal alterations remains insufficiently understood. Methods: The synchronized proteomic and phosphoproteomic profiling of the hippocampus and retina was performed in APP/PS1/MAPT transgenic mice. Differentially expressed proteins (DEPs), differentially phosphorylated peptides (DPPs), enriched pathways, and kinase perturbations were systematically analyzed to distinguish disease-related and age-related molecular patterns. Results: The retina displayed earlier and broader AD-related molecular alterations than the hippocampus. Retinal AD-related DEPs, DPPs and kinase perturbations were enriched in metabolic and molecular pathways, whereas hippocampal AD-related molecules were associated with synapse/axon/neuroactive ligand-related pathways. Two tissues shared a restricted set of dysregulated molecules, including RTN4, HDAC6 and PALS1_S84, Conclusion: This study establishes a synchronized dual-tissue, dual-omics framework for dissecting AD-related pathology and age-associated remodeling, providing new insight into eye-brain molecular crosstalk and offering a theoretical basis for retina-based, noninvasive early diagnosis of AD.Wed Jun 17 00:00:00 GMT+01:00 2026PXD07985010090