Genotype-related changes of ganglioside composition in brain regions of transgenic mouse models of Alzheimer's disease

Abstract

In this study, brain gangliosides of different transgenic mouse models of Alzheimer's disease (AD) were analyzed and compared with age-matched wild-type mice. Gangliosides were analyzed in cerebral cortex, a region with extensive Aβ plaques, and cerebellum, a non-vulnerable region with no Aβ containing plaques. There was a marked increase in simple gangliosides GM2 and GM3 only within the cortex of all mice expressing APP SL. Additionally, loss of complex “a” gangliosides (GT1a, GD1a and GM1) was recorded in APP/PS1Ki model, whereas in APP SL and APP/PS1 mice, the complex “b” gangliosides (GQ1b, GT1b and GD1b) moderately decreased. Surprisingly, expression of either mutant PS1 M146L or PS1 mutant FAD (Ki model) alone tended to lower the levels of both GM2 and GM3 within the cortex. Conversely, only slight changes of the ganglioside pattern were found in the cerebellum. Because ganglioside alterations occurring in APP transgenic mice were similar to those observed in human AD brain, these transgenic models would represent valuable tools to further investigate the role of altered ganglioside metabolism in the pathogenesis of AD.