The amyloid precursor protein and the proteases cleaving this protein are important players in the pathogenesis of Alzheimer's disease via the generation of the amyloid peptide. Physiologically, the amyloid precursor protein is implied in axonal vesicular trafficking and the proteases are implicated in developmentally important signaling pathways, most significantly those involving regulated intramembrane proteolysis or RIP. We discuss the cell biology behind the amyloid and tangle hypothesis for Alzheimer's disease, drawing on the many links to the fields of cell biology and developmental biology that have been established in the recent years.