CALCIUM REGULATES PROCESSING OF THE ALZHEIMER AMYLOID PROTEIN-PRECURSOR IN A PROTEIN-KINASE C-INDEPENDENT MANNER

Various first messengers linked to phospholipase C, including acetylch oline and interleukin 1, regulate the production both of the secreted form of the amyloid protein precursor (APP) and of amyloid beta-protei n. We have now identified intracellular signals which are responsible for mediating these effects. We show that activation of phospholipase C may affect APP processing by either of two pathways, one involving a n increase in protein kinase C and the other an increase in cytoplasmi c calcium levels. The effects of calcium on APP processing appear to b e independent of protein kinase C activation. The observed effects of calcium on APP processing may be of therapeutic utility.