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

Thematic Review Series: Sphingolipids. Role of ganglioside metabolism in the pathogenesis of Alzheimer's disease—a review

“…Interestingly, although cortical levels of GM2 and GM3 are expressed at very low levels in wild-type mouse cortex, they were reduced even further in both PSEN1 mutant lines in the absence of the APP SL transgene. Thus, ganglioside alterations occurring in mice expressing the human mutant APP SL transgene with or without a PSEN1 mutation, but not with a PSEN1 mutation alone, are similar to those observed in humans with AD (23,28,39). In contrast to the robust changes in the cortex, only slight changes in the ganglioside pattern were found in the cerebellum in the PSEN1 and APP/PSEN1 mutant lines (40).…”

“…Although the amount of gangliosides and their patterns are similar in control and in AD cases (37), an observation was made that the A2B5 antibody reacted with human brain c-series gangliosides and, unexpectedly, sulfatides (38). The brain gangliosides of different transgenic mouse models of AD have been analyzed and compared with those of age-matched wild-type mice (39)(40)(41)(42). Barrier et al (39) observed a marked increase in the simple gangliosides GM2 and GM3 in the cortex of 2-year-old APP SL mice expressing the Swedish (K670N/M671L) and London (V717I) mutations of human APP.…”

“…The brain gangliosides of different transgenic mouse models of AD have been analyzed and compared with those of age-matched wild-type mice (39)(40)(41)(42). Barrier et al (39) observed a marked increase in the simple gangliosides GM2 and GM3 in the cortex of 2-year-old APP SL mice expressing the Swedish (K670N/M671L) and London (V717I) mutations of human APP. The proportions of GQ1b, GD1b, GD3, and GT1a were all moderately but significantly decreased in these mice, compared with wild-type controls.…”

“…Thus the cognitive effects of the ganglioside alterations are probably attributable to reduced Ab oligomerization in these mice, secondary to lower levels of APP protein and reduced Ab-binding substrate (b-series gangliosides). These transgenic models represent valuable tools for further investigation of the role of altered ganglioside metabolism in the pathogenesis and treatment of AD (39,40).…”

Ganglioside accumulation in activated glia in the developing brain: comparison between WT and GalNAcT KO mice

“…In addition, accumulation of GM2 has been observed in neurodegenerative diseases such as Alzheimer disease (31)(32)(33) and Angelmanlike syndrome ( 34 ), and in rodent acute brain injury models such as blast-induced mild traumatic brain injury ( 35 ) and a transient focal cerebral ischemia model ( 36 ). However, the mechanisms behind and the roles of accumulated GM2 have not been well elucidated.…”