Open AccessNerve growth factor potentiates the neurotoxicity of beta amyloid.
Author(s) -
Bruce A. Yankner,
Alfredo Cáceres,
Lawrence K. Duffy
Publication year - 1990
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.87.22.9020
Subject(s) - nerve growth factor , neurotoxicity , basal forebrain , cholinergic neuron , hippocampal formation , endocrinology , neurotoxin , alzheimer's disease , neurotrophin , cholinergic , medicine , amyloid beta , amyloid (mycology) , beta (programming language) , neuroscience , biology , receptor , toxicity , disease , botany , computer science , programming language
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.