Remarkably, several upregulated LR interactions from microglia to astrocytes were identified, including C3-CD81 and LR interactions with ligands encoded by APOE and PSAP. Particularly, complement component 3 (C3) and its receptor CD81 molecule (CD81) are recognized for their neuroinflammatory function between microglia and astrocytes, suggesting potential implications in AD pathophysiology (Fig. 2c, Additional file 1: Fig. S2c) [52, 53]. Here, APOE is linked to Alzheimer disease.