In some cases, a PTM is obligate for the formation of a specific protein aggregate, for example, beta- and gamma- secretase cleavage of amyloid precursor protein is widely thought to be a necessary prerequisite to the formation of extracellular beta-amyloid-containing plaques that are a hallmark of AD, but which do not contain intact amyloid precursor protein, and rather only 40–42 residues of post-translationally cleaved sequence [91]. This evidence concerns the gene APP and Alzheimer disease.