Altered apolipoprotein E glycosylation is associated with Aβ(42) accumulation in an animal model of Niemann‐Pick Type C disease

• Published in: Journal of neurochemistry Vol. 112; no. 6; pp. 1619 - 1626
• Main Authors: Chua, Ching‐Ching, Lim, Mei‐Li, Wong, Boon‐Seng
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.03.2010; Wiley-Blackwell
• Subjects: amyloid; apolipoprotein E; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Errors of metabolism; glycosylation; lectin ELISA; Lipids (lysosomal enzyme disorders, storage diseases); Medical sciences; Metabolic diseases; neurodegeneration; Neurology; Niemman‐Pick Type C; NPC1; Niemann-Pick disease; Animal model; Alzheimer disease; Central nervous system; Alteration; neurodegeneration; Lipids; Clearance; Enzymopathy; Encephalon; Apolipoprotein E; lectin ELISA; Genetics; Degenerative disease; Lipoidosis; Nervous system diseases; Niemman-Pick Type C; Rodentia; Metabolic diseases; glycosylation; Metabolism; Cholesterol; Genetic disease; Cerebral disorder; Vertebrata; Mammalia; Storage; amyloid; Mouse; NPC1; Central nervous system disease; Catabolism
• DOI: 10.1111/j.1471-4159.2010.06586.x
• ISSN: 0022-3042

J. Neurochem. (2010) 112, 1619–1626. 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‐β (Aβ) deposition. Apolipoprotein E (apoE) is highly expressed in the brain and plays a pivotal role in cholesterol metabolism. ApoE can also modulate Aβ 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 Aβ catabolism is unclear. In this study using an NPC animal model, we detect specific changes in apoE glycosylation that correlate with increased Aβ(42) accumulation prior to the appearance of neurological abnormalities. This suggests that increased apoE expression could be a compensatory response to the increased Aβ(42) deposition in NPCnih mice. We also observe what appears to be a simplification of the glycosylation process on apoE during neurodegeneration.