Nerve growth factor potentiates the neurotoxicity of beta amyloid.
The role of growth factors in the pathogenesis of Alzheimer disease is unknown. The beta-amyloid protein accumulates abnormally in the brain in Alzheimer disease and is neurotoxic to differentiated hippocampal neurons in culture. Nerve growth factor (NGF) increased the neurotoxic potency of a beta-amyloid polypeptide by a factor of approximately 100,000, which resulted in a reduction of the beta-amyloid neurotoxic EC50 from 0.1 microM to 1 pM. This potentiating effect of NGF was reversed by a monoclonal antibody against NGF and was not observed for a variety of other neurotrophic growth factors. Exposure of hippocampal neurons to very low concentrations of beta amyloid alone resulted in a marked induction of immunoreactive NGF receptors. Addition of NGF with beta amyloid resulted in the appearance of neurodegenerative changes in NGF receptor-positive neurons. The early and profound degeneration of hippocampal and basal forebrain cholinergic neurons that occurs in Alzheimer disease may result from a neurotoxic interaction of beta amyloid with NGF.
Yankner
B A
BA
Department of Neurology, Harvard Medical School, Boston, MA 02115.
Caceres
A
A
Duffy
L K
LK
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D017475:Receptors, Nerve Growth Factor
D016229:Amyloid beta-Peptides; D009414:Nerve Growth Factors; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor