Indeed, synaptic dysfunction and abnormal behaviors in transgenic murine models are apparent in mice lacking adequate SHANK3; in the CNS of the transgenic AD (TgAD) 5x familial AD murine model engineered to overexpress the 42 amino acid amyloid-beta (Aβ42) peptide, SHANK3 was also found to be significantly downregulated but the pathological mechanisms remain unclear (9, 10, 12, 21, 25–27). Here, SHANK3 is linked to Alzheimer disease.