This study utilized the P6 probe to specifically capture protein components deposited within cerebral amyloid plaques from 5XFAD transgenic Alzheimer’s disease model mice. Wild-type (WT) mouse brain tissues were processed in parallel as negative controls to subtract non-specific background binding signals derived from the probe pulldown assay. Captured protein complexes were digested with trypsin, fractionated via liquid chromatography, and profiled using high-resolution LC-MS/MS proteomic technology. Subsequent differential protein screening and functional enrichment analyses were carried out to discover unreported plaque-enriched proteins linked to amyloid aggregation and progressive neurodegeneration. All raw mass spectrometry spectra and peptide identification datasets are archived in this repository to ensure experimental reproducibility and facilitate subsequent mechanistic investigations.