APP and Alzheimer disease: In sporadic AD, the overall level of Aβ may be not significantly elevated, but the following factors may lead to localized Aβ aggregation affecting APP transport: (1) free radicals covalently bind to Aβ, forming localized nuclei or seed crystals which aggregate within cells and inhibit APP transport; (2) positively charged proteins such as heparan sulfate proteoglycans can accelerate Aβ aggregation; and (3) specific intracellular locations of serum amyloid component P, composed of two identical pentamers with each molecule having 10 Aβ-binding sites, can lead to local Aβ aggregation [260].