title: Ganglioside and related-sphingolipid profiles are altered in a cellular model of Alzheimer's disease.
abstract: Sphingolipid-related issues are increasingly discussed to contribute to the neuropathological process of Alzheimer's disease (AD). In this study, gangliosides and related-sphingolipids (ceramides, neutral glycosphingolipids and sphingomyelins) were analyzed in neuroglioma (H4) cells expressing the Swedish mutation of the human amyloid precursor protein (H4APPsw) and compared with those of wild-type control H4 cells. These cells were chosen since H4APPsw cells were previously reported to reproduce well some essential features of AD. We found that H4APPsw cells exhibited a striking elevation of the simplest ganglioside GM3, an abnormality that was consistently reported in AD patients and animal models of AD. Concomitantly, the levels of both lactosylceramide (the immediate metabolic precursor of GM3) and ganglioside GD1a increased, suggesting a deregulation in the biosynthesis of gangliosides in the H4APPsw cells. Moreover, while the total ceramide level remained unaltered in H4APPsw cells, a shift in ceramide composition from long chain - to very long chain fatty acid-ceramide species was recorded. Because sphingolipid alterations occurring in H4APPsw cells were similar to those observed in transgenic mice and in human brains, this cellular model might be useful to further explore the complex role of sphingolipids in AD pathogenesis.
authors.affiliation: Université Laval, Faculté de médecine, Département de Psychiatrie et Neurosciences, Québec, QC, Canada; Centre Hospitalier de l'Université Laval, Axe Neurosciences, Québec, Canada; Université de Poitiers, GRéViC EA3808, Poitiers, France.
authors.forename: Anastasia
authors.initials: A
authors.lastname: Noel
authors.affiliation: Université de Poitiers, UFR Médecine & Pharmacie, Service de Biochimie et Toxicologie, Poitiers, France.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ingrand
authors.affiliation: Université de Poitiers, UFR Médecine & Pharmacie, Service de Biochimie et Toxicologie, Poitiers, France. Electronic address: lbarrier@univ-poitiers.fr.
authors.forename: Laurence
authors.initials: L
authors.lastname: Barrier
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002518:Ceramides / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D009154:Mutation / Q000235:genetics; D013107:Sphingolipids / Q000378:metabolism*
chemical_list: D016564:Amyloid beta-Protein Precursor; D002518:Ceramides; D005732:Gangliosides; D013107:Sphingolipids
keywords: Alzheimer's disease; Cellular model; Ceramides; Gangliosides; Sphingolipids