ARC and Alzheimer disease: In this report we show that the AS-associated protein, Ube3A, a key E3 ligase regulating the degradation of Arc and Ephexin-521,25,45, is downregulated in cognitively impaired AD transgenic mouse brains, and in cultured primary rat hippocampal neurons treated with oligomeric Aβ, suggesting that Ube3A may also be a key player in AD-associated synaptic dysfunction.