Evaluation of white matter integrity in ex vivo brains of amyloid plaque-bearing APPsw transgenic mice using magnetic resonance diffusion tensor imaging

Abstract

Magnetic resonance diffusion tensor imaging (DTI) was used to examine the integrity of midline white matter tracts in APPsw (Tg2576) transgenic mice, a mouse-model of cerebral amyloid deposition. Ex vivo DTI was performed on formalin-fixed brains from APPsw and age-matched transgene-negative control mice at the ages of 12, 15, and 17 months. The characteristics of water diffusion in six midline white matter tracts were quantified using four metrics: relative anisotropy (RA), mean diffusivity, axial diffusivity, and radial diffusivity. Two-way ANOVA analyses indicated a significant main effect of transgene on RA in the corpus callosum (CC) and ventral hippocampal commissure (VHC), due to small reductions (2-6%) in RA in APPsw mice relative to age-matched control mice. However, these reductions were not significant at any specific age group and were not progressive with increasing age. The other diffusion metrics exhibited no significant differences between APPsw and control mice in the CC and VHC, nor did any of the diffusion metrics exhibit significant differences between APPsw and control mice in other midline white matter tracts (anterior commissure, posterior commissure, fornix, and dorsal fornix). Overall, these results indicate that white matter integrity, as measured by ex vivo DTI, is predominately unaltered in formalin-fixed brains from amyloid plaque-bearing APPsw mice.