Increased Tau Phosphorylation and Impaired Presynaptic Function in Hypertriglyceridemic ApoB-100 Transgenic Mice |
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Authors: | Nikolett Lénárt Viktor Szegedi Gábor Juhász Aniko Kasztner János Horváth Erika Bereczki Melinda E. Tóth Botond Penke Miklós Sántha |
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Affiliation: | 1. Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.; 2. Bay Zoltan Foundation for Applied Research, Institute for Plant Genomics, Human Biotechnology and Bioenergy, Szeged, Hungary.; 3. Institute of Medical Chemistry, Faculty of Medicine, University of Szeged, Szeged, Hungary.; Alexander Flemming Biomedical Sciences Research Center, Greece, |
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Abstract: | AimsApoB-100 is the major protein component of cholesterol- and triglyceride-rich LDL and VLDL lipoproteins in the serum. Previously, we generated and partially described transgenic mice overexpressing the human ApoB-100 protein. Here, we further characterize this transgenic strain in order to reveal a possible link between hypeprlipidemia and neurodegeneration.Methods and ResultsWe analyzed the serum and cerebral lipid profiles, tau phosphorylation patterns, amyloid plaque-formation, neuronal apoptosis and synaptic plasticity of young (3 month old), adult (6 month old) and aging (10–11 month old) transgenic mice. We show that ApoB-100 transgenic animals present i) elevated serum and cerebral levels of triglycerides and ApoB-100, ii) increased cerebral tau phosphorylation at phosphosites Ser199, Ser199/202, Ser396 and Ser404. Furthermore, we demonstrate, that tau hyperphosphorylation is accompanied by impaired presynaptic function, long-term potentiation and widespread hippocampal neuronal apoptosis.ConclusionsThe results presented here indicate that elevated ApoB-100 level and the consequent chronic hypertriglyceridemia may lead to impaired neuronal function and neurodegeneration, possibly via hyperphosphorylation of tau protein. On account of their specific phenotype, ApoB-100 transgenic mice may be considered a versatile model of hyperlipidemia-induced age-related neurodegeneration. |
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