PHYSIOLOGICAL LEVELS OF BETA-AMYLOID PEPTIDE PROMOTE PC12 CELL-PROLIFERATION

Alzheimer's beta-amyloid peptide (A beta) is normally present at a sub nanomolar (225-625 pM) concentration in body fluids and in the medium of cultured cells. The potential actions of physiologic levels of A be ta are being investigated. We have recently shown that nanomolar doses of A beta can stimulate tyrosine phosphorylation and activate phospha tidylinositol-3-kinase in neuronal cells. Here we show evidence that A beta at nanomolar levels promotes cell growth determined by [H-3]thym idine incorporation, protein content and cell counts. Physiological le vels of A beta peptides, including 1-40, 1-42, 25-35, all promote grow th of PC12 cells in low serum medium with doubling times of 71 h to ar ound 30 h. Although the promotion of cell proliferation can be detecte d at nanomolar levels of A beta, its potency is less than that of seru m. This suggests that A beta may normally play a neurotrophic/mitogeni c role in neuronal biology.