In late-onset sporadic Alzheimer’s disease (AD), the most prevalent and strongest risk factor is the ε4 allele of the apolipoprotein E (APOE4). To investigate the pathophysiological effects of the APOE4 genotype in the human cellular context, we generated isogenic iPSC-derived astrocytes bearing APOE4 alleles from APOE3 control iPSC. Next, to identify astrocytic APOE4-specific secreted proteomes, we performed a mass spectrometry using culture media from human astrocytes carrying APOE3 or APOE4.