Induction of vascular amyloidosis-β by oxidative stress depends on APOE genotype

Bozena Mazur-Kolecka, Dennis Dickson, Janusz Frackowiak

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


The reduced antioxidant defense in apolipoprotein E ε4/ε4 carriers may contribute to β-amyloidosis. Previously we found that Fe2+-induced oxidative stress caused greater protein oxidation in ε4/ε4 than in ε3/ε3 human brain vascular smooth muscle cells. Moreover, Fe2+ induced lysosomal accumulation of endogenous Aβ and APOE in cultured cells, and Aβ deposition in vascular tunica media in organotypic cultures of brain vessels. Here we demonstrated that Fe2+ enhanced an uptake of exogenous Aβ 1-40 and its deposition together with APOE in lysosomes in myocytes. Aβ deposits were associated with lipid-peroxidation and protein ubiquitination, and were more abundant and stable in ε4/ε4 than in ε3/ε3 cells. In organotypic cultures of brain vessels Fe2+ induced deposition of non-fibrillar and fibrillar Aβ 1-40 in vascular tunica media. We hypothesize that locally increased concentrations of iron induce accumulation of exogenous and endogenous Aβ in SMCs, triggering β-amyloid angiopathy. The greater susceptibility of ε4 carriers to Fe2+ ions may result in an increased risk of β-amyloidosis.

Original languageEnglish (US)
Pages (from-to)804-814
Number of pages11
JournalNeurobiology of aging
Issue number6
StatePublished - Jun 1 2006


  • APOE genotype
  • Brain vessels culture
  • Cell culture
  • Oxidation
  • β-Amyloid angiopathy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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