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Effect of genetic polymorphism on apolipoprotein E glycosylation and lipoproteins metabolism
Author(s) -
Chua Ching Ching,
ONG QiRui,
WONG BoonSeng
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.823.14
Subject(s) - apolipoprotein e , allele , gene isoform , biology , glycosylation , apolipoprotein b , lipoprotein , endocrinology , medicine , genetics , cholesterol , disease , gene
Alzheimer's disease (AD) is the leading cause of age‐related dementia and apolipoprotein E (ApoE) is a well‐established genetic risk factor in sporadic AD. ApoE is highly expressed in liver and brain, and has an important role in cholesterol metabolism. In human, there are three alleles (E2, E3 and E4). ApoE4 increases disease susceptibility by binding amyloid‐β (Aβ) and preventing their clearance, leading to Aβ accumulation. ApoE3 is the most common allele but ApoE2 is found to reduce AD risk. ApoE is also associated with hypercholesterolemia, a risk factor for AD. However, the mechanisms underlying ApoE role in AD pathology is poorly understood. ApoE undergoes O‐linked glycosylation and various glycosylated isoforms exist. This diversity is partly due to differential sialylation but the effect and identity of this chemical modification on ApoE function and between ApoE isoforms is unknown. In this study, we will present the glycan profile on different ApoE isoforms. We will also demonstrate ApoE contribution to the biochemical profile of high‐density lipoprotein (HDL), LDL, triglycerides and cholesterol as well as their effect on the expression of several enzymes involved in Aβ metabolism.