title: Reduced molecular size and altered disaccharide composition of cerebral chondroitin sulfate upon Alzheimer's pathogenesis in mice.
abstract: Alzheimer's disease (AD) is a progressive disorder leading to cognitive impairment and neuronal loss. Cerebral extracellular accumulation and deposition of amyloid ß plaques is a pathological hallmark of AD. Chondroitin sulfate (CS) is an extracellular component abundant in the brain. CS is a sulfated glycosaminoglycan covalently attached to a core protein, forming chondroitin sulfate proteoglycan. The structure of CS is heterogeneous with sulfation modification and elongation of the chain. The structural diversity of CS allows it to play various roles in the brain. Increasing evidence has shown that CS promotes aggregation of amyloid ß peptides into higher-order species such as insoluble amyloid ß fibrils. Difficulties in the structural analysis of brain CS, as well as its heterogeneity, limit the study of potential roles of CS in AD pathology. Here we established a microanalysis method with reversed-phase ion-pair high performance liquid chromatography and found that CS in the brains of Tg2576 AD model mice show a lower molecular size and an increased ratio of CS-B motif di-sulfated disaccharide. Our findings provide insight into the structural changes of cerebral CS upon Alzheimer's pathogenesis.
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Zui
authors: Z
authors: Zhang
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Shiori
authors: S
authors: Ohtake-Niimi
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kenji
authors: K
authors: Kadomatsu
authors: Department of Biochemistry, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors: Kenji
authors: K
authors: Uchimura
mesh_terms: D000544:Alzheimer Disease; D016229:Amyloid beta-Peptides; D000818:Animals; D002809:Chondroitin Sulfates; D004187:Disaccharides; D051379:Mice; D008810:Mice, Inbred C57BL; D058225:Plaque, Amyloid
chemical_list: D016229:Amyloid beta-Peptides; D004187:Disaccharides; D002809:Chondroitin Sulfates
keywords: Alzheimer’s disease; HPLC; chondroitin sulfate; neurodegeneration