Increased Tau Phosphorylation and Impaired Presynaptic Function in Hypertriglyceridemic ApoB-100 Transgenic Mice

Lénárt, Nikolett and Szegedi, Viktor and Juhász, Gábor and Kasztner, Anikó and Horváth, János and Bereczki, Erika and Tóth, Erzsébet Melinda and Penke, Botond and Sántha, Miklós (2012) Increased Tau Phosphorylation and Impaired Presynaptic Function in Hypertriglyceridemic ApoB-100 Transgenic Mice. PLOS ONE, 7 (9). ISSN 1932-6203

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Abstract

Aims: ApoB-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 Results: We 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 Ser 199, Ser 199/202, Ser 396 and Ser 404. Furthermore, we demonstrate, that tau hyperphosphorylation is accompanied by impaired presynaptic function, long-term potentiation and widespread hippocampal neuronal apoptosis. Conclusions: The 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. © 2012 Lénárt et al.

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