Based upon the results from this study and the discussion above, we developed a working hypothesis of GJA1 dysregulation in AD (Fig. 11), in which upregulation of GJA1, a master regulator of astrocytic gene expression, concomitant with amyloid accumulation during Alzheimer pathogenesis ultimately drives AD clinical and pathological traits as evidenced by highly significant correlation with AD progression and AD GWAS genes (Fig. 2a-g). The gene discussed is GJA1; the disease is Alzheimer disease.