BACULOVIRUS-INFECTED CELLS DO NOT PRODUCE THE AMYLOID PEPTIDE OF ALZHEIMERS-DISEASE FROM ITS PRECURSOR

The amyloid peptide (A beta) of Alzheimer's disease (AD) is produced b y proteolytic cleavage of a larger precursor, the amyloid peptide prec ursor or APP, The discovery of pathogenic mutations in the APP gene pr ovides strong evidence for the hypothesis that APP metabolism is invol ved in the etiology of AD, To study the metabolism of the protein, hum an APP has been expressed in several mammalian cell types, Insect cell s, infected by a recombinant baculovirus carrying the human APP sequen ce, also provide an interesting expression system because these cells do not produce endogenous APP, Baculovirus-infected cells synthesize v ery high amounts of extracellular soluble APP, after cleavage of the t ransmembrane protein, as described for mammalian cells, However, we de monstrate here that insect cells do not produce A beta from APP, These results suggest that while the enzymatic activity needed for the prod uction of soluble APP is conserved between insect and mammalian cells, the enzymes required for the production of A beta from APP are only e xpressed in mammalian cells.