Secretion of Alzheimer beta/A4 protein (1-40) and intracellular retention of beta/A4 protein (1-42) in transfected COS cells.

The amyloid beta/A4 protein (beta/A4) of Alzheimer disease is heterogeneous. A beta 1-40 (Asp1 to Val40) is rather soluble, whereas A beta 1-42 (Asp1 to Ala42) is more insoluble and can be the seed of deposition of A beta 1-40. Although beta/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 A beta 1-40 was secreted, whereas A beta 1-42 was hardly secreted. A beta 1-40 secretion was not inhibited by metabolic inhibitors such as brefeldin A. The normally produced A beta 1-40 could not be retained intracellularly, whereas the abnormally generated A beta 1-42 might be accumulated intracellularly, resulting in cellular toxicity.