SMAD3 and Alzheimer disease: Reduced levels of Smad3 and impairment of Smad3 signaling have been observed in the AD brain, associated with increased Aβ accumulation, Aβ-induced neurodegeneration and neurofibrillary tangle formation (Luterman et al., 2000; Colangelo et al., 2002; Katsel et al., 2005; Tesseur et al., 2006).