Altered sphingolipid metabolism plays an emergent role in the etiology of Alzheimer's disease (AD). In this study, we determined the levels of ceramides and other related-sphingolipids (sphingomyelins, sulfatides and galactosylceramides) in the cerebral cortex of an APP(SL)/PS1Ki mouse model of AD. The results demonstrate that ceramides accumulated in the cortex of APP(SL)/PS1Ki mice, but not in PS1Ki mice, whereas all others major sphingolipids (except galactosylceramides) were not altered in comparison with those from age-matched wild-type mice. Furthermore, as early as 3 months of age, female mice but not males, exhibit a strong increase in 2-hydroxy fatty acid-containing ceramides, whereas males display a significant elevation of non-hydroxy fatty acid ceramide species. Therefore, the gender differences in ceramide accumulation in the brain of mice expressing APP(SL) suggest that additional factors like modified ceramide metabolism may contribute to the increased propensity of females to develop AD.
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Ceramide and Related-Sphingolipid Levels Are Not Altered in Disease-Associated Brain Regions of APP and APP/PS1 Mouse Models of Alzheimer's Disease: Relationship with the Lack of Neurodegeneration?
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Groupe de Recherche sur le Vieillissement Cérébral, GreViC EA 3808, Faculté de Médecine et de Pharmacie, 6 rue de la Milétrie, BP 199, 86034 Poitiers Cedex, France.
There is evidence linking sphingolipid abnormalities, APP processing, and neuronal death in Alzheimer's disease (AD). We previously reported a strong elevation of ceramide levels in the brain of the APP(SL)/PS1Ki mouse model of AD, preceding the neuronal death. To extend these findings, we analyzed ceramide and related-sphingolipid contents in brain from two other mouse models (i.
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Groupe de Recherche sur le Vieillissement Cérébral, GreViC EA 3808, Faculté de Médecine et de Pharmacie, 6 rue de la Milétrie, BP 199, 86034 Poitiers Cedex, France.
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