Barrier Laurence, Fauconneau Bernard, Noël Anastasia, Ingrand Sabrina
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.
Int J Alzheimers Dis. 2010 Dec 27;2011:920958. doi: 10.4061/2011/920958.
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.e., APP(SL) and APP(SL)/PS1(M146L)) 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 APP(SL)/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 APP(SL) mice, we hypothesized that it might explain the lack of ceramide accumulation, at least in this model.
有证据表明，阿尔茨海默病（AD）中鞘脂异常、淀粉样前体蛋白（APP）加工和神经元死亡之间存在关联。我们之前报道，在APP（SL）/PS1Ki AD小鼠模型的大脑中，神经酰胺水平在神经元死亡之前显著升高。为了扩展这些发现，我们分析了另外两种小鼠模型（即APP（SL）和APP（SL）/PS1（M146L））大脑中的神经酰胺及相关鞘脂含量，这两种模型的病理时间进程更接近目前大多数可用模型中的情况。与我们之前的研究相反，这两种模型疾病相关脑区（皮层和海马体）中神经酰胺并未积累。然而，APP（SL）/PS1Ki模型因其剧烈的神经元丢失与神经毒性Aβ异构体的强烈积累同时出现而独特，这在其他AD动物模型中并未观察到。由于APP（SL）小鼠既没有神经元丢失，也没有毒性Aβ物种积累，我们推测这可能解释了至少在该模型中神经酰胺缺乏积累的原因。
