In addition to decreased expression of Smad3 in hippocampi of AD patients, hippocampal neurons show increased levels of activated Smad2 (Lee et al., 2006), along with alterations in the subcellular localization of phosphorylated Smad2/3 (Colangelo et al., 2002; Lee et al., 2006), which remains in the cytoplasm of neurons, instead of translocating into the nucleus (Lee et al., 2006; Ueberham et al., 2006). The gene discussed is SMAD3; the disease is Alzheimer disease.