The effects of apolipoproteins E3 and E4 on the transforming growth factor-β system in targeted replacement mice

Adi Haas, Ori Liraz, Daniel M. Michaelson

Research output: Contribution to journalArticlepeer-review

Abstract

Background: This study examined the possibility that apolipoprotein E4 (apoE4), the most prevalent genetic risk factor of Alzheimer's disease, interacts isoform specifically with the transforming growth factor (TGF)-β system. Methods: This was pursued by measurements of the effects of apoE3 and apoE4 on the levels of TGF-β ligands and on activation of the Smad system in brains of human apoE targeted replacement mice, utilizing Western blot. Results: The study revealed that apoE4 reduces, isoform specifically, the levels of TGF-β 1, TGF-β 2 and TGF-β 3 in the septum and of TGF-β 3 in the hippocampus. In contrast, the levels and extent of phosphorylation of Smad1, 5 and 8 as well as of Smad2 and Smad3 in these brain areas were not affected by apoE4, suggesting that the apoE4-driven effects on the TGF-β system may be mediated via the Smad-independent non-canonical pathway. Conclusion: The possible role of the TGF-β system in mediating the pathological effects of apoE4 is discussed.

Original languageEnglish
Pages (from-to)41-45
Number of pages5
JournalNeurodegenerative Diseases
Volume10
Issue number1-4
DOIs
StatePublished - Apr 2012

Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Transforming growth factor-β

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