APOE and Alzheimer disease: In AD, sortilin has been shown to represent a major endocytic pathway for the clearance of apoE/Aβ complexes (Carlo et al., 2013) and to control APP processing to Aβ (Gustafsen et al., 2013), while in fronto-temporal lobar degeneration it has been shown to regulate extracellular levels of progranulin (PGRN; Hu et al., 2010).