Alzheimer-like neurodegeneration in aged anti-Nerve Growth factor transgenic mice

Neurotrophin nerve growth factor (NGF) has been suggested to be involved in age-related neurodegenerative diseases, but no trans- genic model is currently available to study this concept. We have obtained transgenic mice expressing a neutralizing anti-NGF re- combinant 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. Gon\ufb02oni, G. Rossi, N. B. & A. C. (2000) J. Neurosci., 20, 2589\u20132601]. In this paper, we analyze the phenotype of aged anti-NGF transgenic mice and demonstrate that these mice acquire an age-dependent neurodegenerative pathol- ogy including amyloid plaques, insoluble and hyperphosphory- lated t, and neuro\ufb01brillary tangles in cortical and hippocampal neurons. Aged anti-NGF mice also display extensive neuronal loss throughout the cortex, cholinergic de\ufb01cit in the basal forebrain, and behavioral de\ufb01cits. The overall picture is strikingly reminiscent of human Alzheimer\u2019s 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 de\ufb01cit in the signaling and/or transport of NGF leads to neurodegeneratio