Note that SPP1 was also differentially expressed in the DAM-like microglia/macrophage population (Fig. 7D, cluster 13b volcano plot), the same cluster expressing APOE and TREM2. OPN has been recently suggested as an early AD biomarker [141] and its deletion or reduction through anti-OPN antibodies was reported to reduce plaque burden in AD mice suggesting an overall neurotoxic function during AD pathogenesis [142]. The gene discussed is APOE; the disease is Alzheimer disease.