The Amyloid Protein Precursor of Alzheimer's Disease Is a Mediator of the Effects of Nerve Growth Factor on Neurite Outgrowth

The (3A4 protein, the major component of the amyloid deposition characterizing Alzheimer’s disease, derives from the amyloid protein precursor (APP), an integral membrane protein with soluble derivatives. The function of APP is unknown. Both soluble and membraneassociated human brain APP (lo-‘0 M) significantly increased (P < 0.025) neurite length and branching in pheochromocytoma PC12 cells, but did not affect the number of neurites per cell. At higher concentrations, APP was cytotoxic, with a half-maximal concentration of 5 x 10mq M. Nerve growth factor (NGF) is known to affect APP expression in vivo and in vitro. Antibodies to APP specifically diminished the effects of NCF on neurite length and branching. Thus APP may act to mediate neurite outgrowth promotion by NGF.