The amyloid β/A4 protein (β/A4) of Alzheimer disease is heterogeneous. A β1-40 (Asp 1 to Val 4 0 ) is rather soluble, whereas Aβ1-42 (Asp 1 to Ala 4 2 ) is more insoluble and can be the seed of deposition of Aβ1-40. Although β/A4 itself could not be expressed transiently in COS cells by cDNA transfection, it was expressed after directly adding a signal sequence to its N-terminal end. The expressed Aβ1-40 was secreted, whereas Aβ1-42 was hardly secreted. Aβ1-40 secretion was not inhibited by metabolic inhibitors such as brefeldin A. The normally produced Aβ1-40 could not be retained intracellularly, whereas the abnormally generated Aβ1-42 might be accumulated intracellularly, resulting in cellular toxicity.