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
Affiliations: Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, USA
Correspondence:
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Correspondence to: Dr. Erhard Bieberich, Department of Neuroscience and Regenerative Medicine, Medical College of Georgia, Georgia Regents University, 1120 Fifteenth Street, CA4012, Augusta, Georgia, 30912, USA. Tel.: +1 706 721 9113; Fax: +1 706 721 8685; ebieberich@gru.edu
Abstract: 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.
