Physiological levels of beta-amyloid peptide promote PC12 cell proliferation

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