This dataset contains 4D‑DIA quantitative proteomic data from mouse splenic B cells and B‑cell‑conditioned medium (BCM). B‑cells were isolated from young (2‑4 months), old (12‑15 months), AD model (12‑15 months), ATP5D KO (12‑15 months), ATP5D KI (12‑15 months), AD+ATP5D KO (12‑15 months), and AD+ATP5D KI (12‑15 months) mice. BCM samples were collected from young and old mouse B‑cell cultures. Sample preparation including protein extraction, reduction, alkylation, trypsin digestion and desalting was performed. LC‑MS/MS acquisition was carried out on an Orbitrap Q Exactive Plus mass spectrometer. Raw MS files and quantitative proteomics results are deposited in this iProX project. Database searching was performed against the UniProt database for Mus musculus using MaxQuant.