Crosslinking of Apolipoprotein E by Products of Lipid Peroxidation

摘要: Apolipoprotein E (APOE) genotype and advancing aging are interacting ri sk factors in the expression of late onset sporadic Alzheimer's Disease (AD). We tested hypothesis that 2 products lipid peroxidation, malondialdehyde (MDA) 4 hydroxy-2-nonenal (HNE), covalently modify APOE alter its metabolism. In vitro, both HNE MDA crosslinked purified APOE3 APOE4. was a more potent crosslinker than MDA, APO3 susceptible to crosslinking by P19 neuroglial cultures, oxidative stress with peroxidation led increased intracellular accumulation anti-HNE anti-APOE immunoreactive proteins approximately 50 kDa. Intercellular kDa APOE-immunoreactive protein (APOE-50) not prevented cyclohexamide, suggesting formation post-translational mechanisms. CSF, co-migrated most for adducts, containing NaB3H4-reducible bonds. These were CSF from adult subjects (with or without dementia), AD patients homozygous APOE4 alleles. data suggest crosslinks cultures form protein, similar modifications appear occur vivo.