APP and Alzheimer disease: Kinases such as GSK-3, JNK, extracellular signal–regulated kinase (ERK), cdk5, cdk4, and cdc2 phosphorylate this site on APP (Suzuki et al. 1994; Aplin et al. 1996; Iijima et al. 2000; Standen et al. 2001; Muresan and Muresan, 2005; Judge et al. 2011), and studies in AD brains have shown that compromised neurons exhibit activation of these kinases as well as aberrant expression of cyclins B, D, and E (Nagy et al. 1997; Vincent et al. 1997; Busser et al. 1998; Raina et al. 1999).