title: 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.
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.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Dinkins
authors.forename: Somsankar
authors.initials: S
authors.lastname: Dasgupta
authors.forename: Guanghu
authors.initials: G
authors.lastname: Wang
authors.forename: Gu
authors.initials: G
authors.lastname: Zhu
authors.forename: Qian
authors.initials: Q
authors.lastname: He
authors.forename: Ji Na
authors.initials: JN
authors.lastname: Kong
authors.forename: Erhard
authors.initials: E
authors.lastname: Bieberich
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000097:blood* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002518:Ceramides / Q000008:administration & dosage* / Q000276:immunology*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D055354:Exosomes / Q000378:metabolism; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D058225:Plaque, Amyloid / Q000473:pathology* / Q000503:physiopathology; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D002518:Ceramides; D007074:Immunoglobulin G; C492144:Pdcd6ip protein, mouse; D053764:Presenilin-1
keywords: Alzheimer’s disease; amyloid; antibodies; ceramide; exosomes; mice