Neuroanatomical Abnormalities in Behaviorally Characterized APPV717F Transgenic Mice

Abstract

Histological analyses were performed on the brains of APPV717F transgenic (Tg)mice previously studied in a battery of behavioral tests. We describe here the regional and age-dependent deposition of amyloid in both heterozygous and homozygous Tg mice. We also report that Tg mice show significant and age-dependent changes in synaptic density measured by synaptophysin immunoreactivity. Surprisingly, a rather marked hippocampal atrophy is observed as early as 3 months of age in Tg mice (20–40%). Statistical analyses revealed that the deficits in object recognition memory are related to the number of amyloid deposits in specific brain regions, whereas deficits in spatial reference and working memory are related to the changes in synaptic density and hippocampal atrophy. Our study suggests that the behavioral deficits observed in Tg mice are only in part related to amyloid deposition, but are also related to neuroanatomical alterations secondary to overexpression of the APPV717F transgene and independent of amyloid deposition.

Keywords

• transgenic mice
• amyloid precursor protein
• APP
• Alzheimer's disease
• synaptophysin
• synaptic density