| First Author | Lénárt N | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 9 | Pages | e46007 |
| PubMed ID | 23029362 | Mgi Jnum | J:191968 |
| Mgi Id | MGI:5463702 | Doi | 10.1371/journal.pone.0046007 |
| Citation | Lenart N, et al. (2012) Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB-100 transgenic mice. PLoS One 7(9):e46007 |
| abstractText | 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. |
