Amyloid precursor protein and membrane phospholipids in primary cortical neurons increase with development, or after exposure to nerve growth factor or A beta(1-40)

We examined the relationships between membrane phospholipid levels, the sec retion and expression of the amyloid precursor protein (APP), and the respo nses of both to nerve growth factor (NGF), A beta(1-40) or A beta(40-1) in developing cortical neurons cultured from rat embryos. Neuronal membrane ph ospholipid levels per cell, and phosphatidylcholine, phosphatidylserine, ph osphatidylinositol and phosphatidylethanolamine increased individually betw een the first and seventh days of culturing. The amounts of APP holoprotein and APP mRNAs in the cells, as well as the amounts of soluble APP (APPs) s ecreted by them, also increased during neuronal development in vitro. The i ncreases in APPs exceeded the increases in APP which, in turn, exceed those in phospholipid levels. The levels of APP holoprotein, but not of phosphol ipids, increased when neurons were grown in a choline-free medium, suggesti ng that increases in APP art: not sufficient to stimulate changes in membra ne phospholipids. Treatment of neuron cultures for four days with NGF or A beta(1-40), but not with A beta(40-1), dose-dependently increased membrane phospholipids, tau and GAP-43, as well as APP holoprotein and secreted APPs . These results indicate that agents, like NGF or A beta(1-40), which enhan ce membrane phospholipid levels may promote neurite formation, APP expressi on and APPs secretion in primary neuronal cultures. (C) 2000 Published by E lsevier Science B.V. All rights reserved.