Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB-100 transgenic mice.

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.

• Authors: Nikolett Lénárt, Viktor Szegedi, Gábor Juhász, Aniko Kasztner, János Horváth, Erika Bereczki, Melinda E Tóth, Botond Penke, Miklós Sántha
• Journal: PloS one (PLoS One) Vol. 7 Issue 9 Pg. e46007 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23029362 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein B-100
• Triglycerides
• tau Proteins

Topics

• Aging
• Animals
• Apolipoprotein B-100 (genetics, metabolism)
• Apoptosis
• Brain (metabolism, pathology, physiopathology)
• Electrophysiological Phenomena
• Humans
• Hypertriglyceridemia (blood, cerebrospinal fluid, genetics, metabolism)
• Lipid Metabolism
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuronal Plasticity
• Neurons (cytology, pathology)
• Phosphorylation
• Plaque, Amyloid (genetics, metabolism, pathology)
• Triglycerides (blood, cerebrospinal fluid)
• tau Proteins (metabolism)