Strain specific differences in memory and neuropathology in a mouse model of Alzheimer's disease

Abstract

Aims Studies using transgenic mouse strains that incorporate Alzheimer's disease (AD) mutations are valuable for the identification of signaling pathways, potential drug targets, and possible mechanisms of disease that will aid in our understanding of AD. However, reports on the effects of specific AD mutations (Swedish, KM670/671NL; Indiana, V717F) on behavior (Morris water maze) and neuropathological progression have been inconsistent when comparing different genetic backgrounds in these models. Given this, investigators are compelled to more closely evaluate different background strains. The aim of the present study was to compare two commonly used TgCRND8 backgrounds, the 129SvEvTac/C57F1 strain and the C3H/C57F1 strain. Main methods Memory function was assessed by the Morris water maze, a test for assaying hippocampal-dependent memory. We also stained with ThioflavinS in order to visualize and quantify amyloid beta (Aβ) plaques. Real time polymerase chain reaction (PCR) was used to measure insulin-degrading enzyme (IDE), an enzyme that also degrades amyloid beta. Key findings We found deficits in the 129SvEvTac/C57F1 strain in several parameters of the Morris water maze. In addition, amyloid plaque load expression was significantly greater in the 129SvEvTac/C57F1 as compared to the C3H/C57F1 strain as demonstrated by histochemical staining. We also observed a significant decrease in IDE, in the 129SvEvTac/C57F1 strain. Significance This study supports the notion that strain specific differences are apparent in tests of spatial memory and neuropathologic progression in AD.