Adi Haas1, Ori Liraz, Daniel M Michaelson. 1. Department of Neurobiology, The George S Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
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.
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 humanapoE 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.
Authors: Anat Boehm-Cagan; Roni Bar; Dror Harats; Aviv Shaish; Hana Levkovitz; John K Bielicki; Jan O Johansson; Daniel M Michaelson Journal: PLoS One Date: 2016-11-08 Impact factor: 3.240