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PMID: 2174172 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nerve growth factor potentiates the neurotoxicity of beta amyloid.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 22 ·1990-11-00 ·Pages 9020-3

Yankner BA, Caceres A, Duffy LK

Abstract

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.

MeSH Terms
Amyloid beta-Peptides/toxicity Animals Cell Survival/drug effects Dose-Response Relationship, Drug Drug Synergism Epidermal Growth Factor/pharmacology Fibroblast Growth Factor 2/pharmacology Hippocampus/cytology In Vitro Techniques Nerve Growth Factors/pharmacology Neurons/drug effects Platelet-Derived Growth Factor/pharmacology Rats Receptors, Cell Surface/metabolism Receptors, Nerve Growth Factor
Chemicals
Amyloid beta-Peptides Nerve Growth Factors Platelet-Derived Growth Factor Receptors, Cell Surface Receptors, Nerve Growth Factor Fibroblast Growth Factor 2 Epidermal Growth Factor
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Yankner B A
Department of Neurology, Harvard Medical School, Boston, MA 02115.
Caceres A
Duffy L K
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.22.9020
Published
1990-11-00
Pages
9020-3
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC55092
Subset
IM
Grants
NINDS NIH HHS · K08NS01240 · United States
NIA NIH HHS · R29AG09229 · United States
External Links
PubMed source DOI: 10.1073/pnas.87.22.9020 PMC Full Text View journal details
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