Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice

Simona Capsoni, Gabriele Ugolini, Alessandro Comparini, Francesca Ruberti, Nicoletta Berardi, Antonino Cattaneo

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Neurotrophin nerve growth factor (NGF) has been suggested to be involved in age-related neurodegenerative diseases, but no transgenic model is currently available to study this concept. We have obtained transgenic mice expressing a neutralizing anti-NGF recombinant antibody, in which the levels of antibodies are three orders of magnitude higher in adult than in newborn mice [F.R., S.C., A.C., E. Di Daniel, J. Franzot, S. Gonfloni, G. Rossi, N. B. and A. C. (2000) J. Neurosci., 20, 2589-2601]. In this paper, we analyze the phenotype of aged anti-NGF transgenic mice and demonstrate that these mice acquire an age-dependent neurodegenerative pathology including amyloid plaques, insoluble and hyperphosphorylated τ, and neurofibrillary tangles in cortical and hippocampal neurons. Aged anti-NGF mice also display extensive neuronal loss throughout the cortex, cholinergic deficit in the basal forebrain, and behavioral deficits. The overall picture is strikingly reminiscent of human Alzheimer's disease. Aged anti-NGF mice represent, to our knowledge, the most comprehensive animal model for this severe neurodegenerative disease. Also, these results demonstrate that, in mice, a deficit in the signaling and/or transport of NGF leads to neurodegeneration.

Original languageEnglish
Pages (from-to)6826-6831
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
Publication statusPublished - Jun 6 2000

ASJC Scopus subject areas

  • General
  • Genetics


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