TY - JOUR
T1 - The effects of apolipoproteins E3 and E4 on the transforming growth factor-β system in targeted replacement mice
AU - Haas, Adi
AU - Liraz, Ori
AU - Michaelson, Daniel M.
PY - 2012/4
Y1 - 2012/4
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Apolipoprotein E
KW - Transforming growth factor-β
UR - http://www.scopus.com/inward/record.url?scp=84860221072&partnerID=8YFLogxK
U2 - 10.1159/000334902
DO - 10.1159/000334902
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AN - SCOPUS:84860221072
SN - 1660-2854
VL - 10
SP - 41
EP - 45
JO - Neurodegenerative Diseases
JF - Neurodegenerative Diseases
IS - 1-4
ER -