The Effects of Apolipoproteins E3 and E4 on the Transforming Growth Factor-β System in Targeted Replacement Mice.

Neurodegener Dis. 2012 Feb 1; 10:41-45.


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.

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