The cytoplasmic retention of phosphorylated Smad2/3 and its colocalization with amyloid plaques and neurofibrillary tangles has been observed in the hippocampal neurons in the brains of AD patients, indicating the inhibitory effects of neurofibrillary tangles on TGF-β signaling [104,105]. The gene discussed is TGFB1; the disease is Alzheimer disease.