Fig 2. Diagrammatic representation of APP processing. APP is a transmembrane protein with both extra- and intracellular components. APP is processed by 2 competing pathways. The -secretase pathway generates sAPP and C83 protein by cleavage of the -secretase enzyme (). In the β-secretase pathway, the enzyme β-secretase (β) cleaves APP into an sAPP_β fragment and a C99 fragment. The C99 fragment is further cleaved by -secretase enzyme () into an amyloid β fragment (Aβ) and an AICD fragment. The Aβ fragments polymerize. The oligomers and polymers exhibit neurotoxicity. As polymerization proceeds to more complex forms, senile plaques are developed. The C83 fragment is also further processed. However, the function of its products is not fully understood. (The relative sizes of the protein fragments are not drawn to scale.)