APP and Alzheimer disease: Our previous data from aging rhesus monkeys purport a mechanism by which phosphorylated tau may exacerbate Aβ generation within neurons, similar to how genetic predispositions in retromer (e.g., SORL1) signaling pathways may increase the risk of sporadic AD by triggering “endosomal traffic jams,” increasing the time amyloid precursor protein (APP) spends in endosomes where it is cleaved to Aβ.50