NGF promotes amyloid precursor protein secretion via muscarinic receptor activation.

Processing of beta-amyloid precursor protein (APP) is coupled to several neurotransmitter receptors, including m1 muscarinic (m1AChR), and is associated with decreased amyloid deposition. Muscarinic agonist-stimulated APP secretion and membrane APP were measured in control and in NGF-differentiated PC12 cells stably transfected with m1AChR. This secretion was markedly enhanced following treatment with 50 ng/ml NGF for 3 days, and was observed using either carbachol or the M1-selective agonist AF102B. The effects of NGF were reflected by larger reductions in membrane-associated APP levels following muscarinic stimulation. These observations imply that M1 muscarinic receptors may act in concert with NGF to boost APP processing, and M1-selective agonists may thus be beneficial for reducing amyloid deposition by NGF-responsive neurons.