Ceramide and Related-Sphingolipid Levels Are Not Altered in Disease-Associated Brain Regions of APPSL and APPSL/PS1M146L Mouse Models of Alzheimer's Disease: Relationship with the Lack of Neurodegeneration?

Abstract

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 APPSL/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.e., APPSL and APPSL/PS1M146L) in which the time-course of pathology is closer to that seen in most currently available models. Conversely to our previous work, ceramides did not accumulate in disease-associated brain regions (cortex and hippocampus) from both models. However, the APPSL/PS1Ki model is unique for its drastic neuronal loss coinciding with strong accumulation of neurotoxic Aβ isoforms, not observed in other animal models of AD. Since there are neither neuronal loss nor toxic Aβ species accumulation in APPSL mice, we hypothesized that it might explain the lack of ceramide accumulation, at least in this model.