Altered apolipoprotein E glycosylation is associated with Abeta(42) accumulation in an animal model of Niemann-Pick Type C disease.
Neurodegeneration is the final cause of death in Niemann-Pick Type C (NPC) disease, a cholesterol-storage disorder. Accumulating evidence indicates that NPC may share common pathological mechanisms with Alzheimer's disease, including the link between aberrant cholesterol metabolism and amyloid-beta (Abeta) deposition. Apolipoprotein E (apoE) is highly expressed in the brain and plays a pivotal role in cholesterol metabolism. ApoE can also modulate Abeta production and clearance, and it is a major genetic risk factor for Alzheimer's disease. Although apoE is glycosylated, the functional significance of this chemical alteration on Abeta catabolism is unclear. In this study using an NPC animal model, we detect specific changes in apoE glycosylation that correlate with increased Abeta(42) accumulation prior to the appearance of neurological abnormalities. This suggests that increased apoE expression could be a compensatory response to the increased Abeta(42) deposition in NPC(nih) mice. We also observe what appears to be a simplification of the glycosylation process on apoE during neurodegeneration.
Chua
Ching-Ching
CC
Department of Physiology and National University Medical Institutes, Yong Loo Lin School of Medicine, and Neurobiology Programme, Life Science Institute, National University of Singapore, Singapore.
Lim
Mei-Li
ML
Wong
Boon-Seng
BS
D000367:Age Factors; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006031:Glycosylation; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D000077296:Niemann-Pick C1 Protein; D052556:Niemann-Pick Disease, Type C / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D011506:Proteins / Q000235:genetics
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D047908:Intracellular Signaling Peptides and Proteins; D037102:Lectins; D000077296:Niemann-Pick C1 Protein; C106831:Npc1 protein, mouse; D010446:Peptide Fragments; D011134:Polysaccharides; D011506:Proteins; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42)