For examples, while NEDD8 is normally localized in the nucleus of normal hippocampal pyramidal cells and granule cells, it is mostly located in the cytoplasm of AD hippocampal neurons.291,292 Furthermore, APP (β-amyloid precursor protein) is the precursor of Aβ, which is generated from APP by sequential cleavages by β-secretase and γ-secretase complex. This evidence concerns the gene APP and Alzheimer disease.