APP and Alzheimer disease: We decided to test Ubiquilin 1 because (i) the gene encoding Ubiquilin 1 (UBQLN1) is located in a region of chromosome 9 that displays linkage to AD in several independent samples [41-46], (ii) a polymorphism in UBQLN1 modulates AD risk in several independent samples [47-49], (iii) Ubiquilin 1 can modulate APP trafficking to the cell surface in HEK-293 and H4 cell lines [31], and (iv) Ubiquilin 1 can modulate γ-secretase activity, though the consequences of this modulation on γ-secretase substrates were not determined [32-34].