Artigo Acesso aberto Revisado por pares

Alzheimer-like neurodegeneration in aged antinerve growth factor transgenic mice

2000; National Academy of Sciences; Volume: 97; Issue: 12 Linguagem: Inglês

10.1073/pnas.97.12.6826

ISSN

1091-6490

Autores

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

Tópico(s)

Neurogenesis and neuroplasticity mechanisms

Resumo

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. & 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.

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