SMAD3 and Alzheimer disease: It has been shown that age, the most important risk factor for AD, influences the expression of molecules involved in immunity as well as in cell signaling and transcription factor regulation, such as transforming growth factor-beta and phosphorylated SMAD3 (Mothers against decapentaplegic homolog 3), in the mouse suprachiasmatic (SCN) and paraventricular nuclei, that is, the neuroanatomical areas crucially involved in the maintenance of circadian rhythmicity [34].