In this context, it is especially interesting to note that we recently showed increased levels of STAT3 protein, a key regulator of GFAP expression (38, 39) in the brains of young APOE ε4 carriers, decades before the typical age at onset of sporadic AD (40), suggesting that increased astrocyte reactivity may be an early driver of AD pathogenesis. The gene discussed is APOE; the disease is Alzheimer disease.