This dataset encompasses Xenium data from cortical tissue of six human AD donors, three homozygous for APOE3 and three homozygous for APOE4. After Xenium, the same sections were stained for amyloid beta plaques with methoxy-X04. The raw and processed data from Xenium as well as the full-slide scans from methoxy-X04 and SYTOX Green staining are shared here. This data is associated with "An Exhausted-Like Microglial Population that Accumulates in Aged and APOE4 Genotype Alzheimer’s Brains", from Millet, Ledo et al..