Frontal cortex tissues of double-transgenic APP/PS1 AD mice that were given daily intraperitoneal injections of melatonin at pharmacological concentration of ~10 mg/kg (0.3 mL, 10 μg/μL) for 3 weeks exhibited a significant degradation of Aβ as a result of the SUMOylation of the amyloid precursor protein (APP) intracellular domain (AICD) at lysine 43 by the SUMO E3 ligase protein inhibitor of activated STAT1 (PIAS1) [918]. This evidence concerns the gene APP and Alzheimer disease.