title: Increased tau phosphorylation and impaired presynaptic function in hypertriglyceridemic ApoB-100 transgenic mice.
abstract: OBJECTIVE
  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.
  
  
  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.affiliation: Institute of Biochemistry, Biological Research Centre of the Hungarian Academy of Sciences, Szeged, Hungary.
authors.forename: Nikolett
authors.initials: N
authors.lastname: Lénárt
authors.forename: Viktor
authors.initials: V
authors.lastname: Szegedi
authors.forename: Gábor
authors.initials: G
authors.lastname: Juhász
authors.forename: Aniko
authors.initials: A
authors.lastname: Kasztner
authors.forename: János
authors.initials: J
authors.lastname: Horváth
authors.forename: Erika
authors.initials: E
authors.lastname: Bereczki
authors.forename: Melinda E
authors.initials: ME
authors.lastname: Tóth
authors.forename: Botond
authors.initials: B
authors.lastname: Penke
authors.forename: Miklós
authors.initials: M
authors.lastname: Sántha
mesh_terms: D000375:Aging; D000818:Animals; D053299:Apolipoprotein B-100 / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D055724:Electrophysiological Phenomena; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000473:pathology; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014280:Triglycerides / Q000097:blood / Q000134:cerebrospinal fluid; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D053299:Apolipoprotein B-100; D014280:Triglycerides; D016875:tau Proteins