Oxidative protein damage in cells engaged in β-amyloidosis is related to apoE genotype

The ε4 allele of apolipoprotein E (apoE) is a risk factor for Alzheimer's disease. The reduced antioxidant defense in ε4 carriers is suggested to contribute to β-amyloidosis. We found that oxidative stress induced by treatment with Fe²⁺ ions raised more protein carbonyls in vascular smooth muscle cells isolated from human brains with apoE genotype ε4/ε4 than with 3ε/ε3 and ε3/ε4. Antioxidant vitamin E prevented formation of carbonyls but not in cells with genotype ε4/ε4. Treatment with Fe²⁺ ions induced cellular accumulation of amyloid-β protein (Aβ)-immunoreactive material that co-localized with heme oxygenase, a marker of oxidative stress, and apoE. We hypothesize that the damage caused by oxidation in ε4/ε4 carriers facilitates development of β-amyloidosis.