The 5XFAD Mouse Model of Alzheimer's Disease Exhibits an Age-Dependent Increase in Anti-Ceramide IgG and Exogenous Administration of Ceramide Further Increases Anti-Ceramide Titers and Amyloid Plaque Burden.
The 5XFAD Mouse Model of Alzheimer's Disease Exhibits an Age-Dependent Increase in Anti-Ceramide IgG and Exogenous Administration of Ceramide Further Increases Anti-Ceramide Titers and Amyloid Plaque Burden.
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DOI：
10.3233/jad-150088
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发表时间：
2015
期刊：
影响因子：
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通讯作者：
Bieberich E
中科院分区：
文献类型：
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作者：
Dinkins MB;Dasgupta S;Wang G;Zhu G;He Q;Kong JN;Bieberich E
我们提出的证据表明，5XFAD阿尔茨海默病模型小鼠的神经酰胺抗体出现年龄依赖性增加，这表明阿尔茨海默病病理学中涉及针对神经酰胺的自身免疫。为了测试这一点，我们通过神经酰胺给药增加血清抗神经酰胺IgG（2倍），并分析5XFAD小鼠中的淀粉样蛋白斑块形成。可溶性或总淀粉样蛋白-β水平无差异。然而，与对照组相比，接受神经酰胺的雌性动物的斑块负荷（数量、面积和大小）增加。神经酰胺处理的小鼠显示血清外泌体增加（使用阿利克斯作为标记物高达3倍），表明全身性抗神经酰胺IgG和外泌体水平与增强的斑块形成相关。
We present evidence that 5XFAD Alzheimer's disease model mice develop an age-dependent increase in antibodies against ceramide, suggesting involvement of autoimmunity against ceramide in Alzheimer's disease pathology. To test this, we increased serum anti-ceramide IgG (2-fold) by ceramide administration and analyzed amyloid plaque formation in 5XFAD mice. There were no differences in soluble or total amyloid-β levels. However, females receiving ceramide had increased plaque burden (number, area, and size) compared to controls. Ceramide-treated mice showed an increase of serum exosomes (up to 3-fold using Alix as marker), suggesting that systemic anti-ceramide IgG and exosome levels are correlated with enhanced plaque formation.