Strikingly, the only two downregulated genes, NPTX2 (log2FC = −1.79, Padj = 0.0011) and CBLN4 (log2FC = −2.34, Padj = 0.037), are important regulators of the excitation/inhibition (E/I) balance by promoting the maturation of synapses53, and two prominent early downregulated AD biomarkers54, 55 (Fig. 5a). The gene discussed is CBLN4; the disease is Alzheimer disease.