APOE3/4 astrocytes uniquely showed upregulation in pathways related to post-synaptic scaffold proteins (e.g., DLGAP1, DLG4, DLC1, and SHANK3) and actin assembly at cell junctions, but downregulation of synaptic membrane and neurotransmitter pathways, neurogenesis, and nervous system development in AD. Here, SHANK3 is linked to Alzheimer disease.