RESUMO
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)-ß system. METHODS: This was pursued by measurements of the effects of apoE3 and apoE4 on the levels of TGF-ß 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-ß(1), TGF-ß(2) and TGF-ß(3) in the septum and of TGF-ß(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-ß system may be mediated via the Smad-independent non-canonical pathway. CONCLUSION: The possible role of the TGF-ß system in mediating the pathological effects of apoE4 is discussed.