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Research Article Free access | 10.1172/JCI119772

Binding of beta-amyloid to the p75 neurotrophin receptor induces apoptosis. A possible mechanism for Alzheimer's disease.

M Yaar, S Zhai, P F Pilch, S M Doyle, P B Eisenhauer, R E Fine, and B A Gilchrest

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Yaar, M. in: PubMed | Google Scholar

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Zhai, S. in: PubMed | Google Scholar

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Pilch, P. in: PubMed | Google Scholar

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Doyle, S. in: PubMed | Google Scholar

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Eisenhauer, P. in: PubMed | Google Scholar

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Fine, R. in: PubMed | Google Scholar

Boston University School of Medicine, Department of Dermatology, Massachusetts 02118-2394, USA.

Find articles by Gilchrest, B. in: PubMed | Google Scholar

Published November 1, 1997 - More info

Published in Volume 100, Issue 9 on November 1, 1997
J Clin Invest. 1997;100(9):2333–2340. https://doi.org/10.1172/JCI119772.
© 1997 The American Society for Clinical Investigation
Published November 1, 1997 - Version history
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Abstract

Alzheimer's disease is a neurodegenerative disorder characterized by the extracellular deposition in the brain of aggregated beta-amyloid peptide, presumed to play a pathogenic role, and by preferential loss of neurons that express the 75-kD neurotrophin receptor (p75NTR). Using rat cortical neurons and NIH-3T3 cell line engineered to stably express p75NTR, we find that the beta-amyloid peptide specifically binds the p75NTR. Furthermore, 3T3 cells expressing p75NTR, but not wild-type control cells lacking the receptor, undergo apoptosis in the presence of aggregated beta-amyloid. Normal neural crest-derived melanocytes that express physiologic levels of p75NTR undergo apoptosis in the presence of aggregated beta-amyloid, but not in the presence of control peptide synthesized in reverse. These data imply that neuronal death in Alzheimer's disease is mediated, at least in part, by the interaction of beta-amyloid with p75NTR, and suggest new targets for therapeutic intervention.

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