The apolipoprotein E (APOE) e4 allele is known to be the strongest genetic risk factor for the development of Alzheimer’s disease. Previous studies have demonstrated that apoE, encoded by the APOE gene, affects Aβ deposition in a dose-, species-, and isoform-dependent manner; however, the detailed molecular mechanisms remain unclear. We recently demonstrated that soluble Aβ species (> 150 kDa) in the brains of Alzheimer’s disease patients act as key aggregation seeds in β-amyloidosis. In this study, using mass spectrometry analysis, we identified apoE as an interactor of these Aβ species.