This C-terminal APP proteolytic cleavage is markedly increased in early stages of AD as related to Braak staging (Braak and Braak, 1997); increased staining is seen in the hippocampal region and around some plaque and tangle-like structures as well as in peri- and intra- neuronal regions of AD brains, whereas minimal reactivity is seen in age-matched control patients (Banwait et al., 2008). The gene discussed is APP; the disease is Alzheimer disease.