Neuroanatomical abnormalities in behaviorally characterized App(V717F) transgenic mice

Histological analyses were performed on the brains of App(V717F) transgenic (Tg) mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozy gous and homozygous Tg mice. We also report that Tg mice show significant a nd age-dependent changes in synaptic density measured by synaptophysin immu noreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20-40%). Statistical analyses reve aled that the deficits in object recognition memory are related to the numb er of amyloid deposits in specific brain regions, whereas deficits in spati al reference and working memory are related to the changes in synaptic dens ity and hippocampal atrophy. Our study suggests that the behavioral deficit s observed in Tg mice are only in part related to amyloid deposition, but a re also related to neuroanatomical alterations secondary to overexpression of the App(V717F) transgene and independent of amyloid deposition. (C) 2000 Academia Press.