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Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice

(2000) AMERICAN JOURNAL OF PATHOLOGY. 156(3). p.951-964
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Abstract
Epidemiological studies have established that the epsilon 4 allele of the ApoE gene (ApoE4) constitutes an important risk factor for Alzheimer's disease and might influence the outcome of central nervous system injury. The mechanism by which ApoE4 contributes to the development of neurodegeneration remains unknown. To test one hypothesis or mode of action of ApoE, we generated transgenic mice that overexpressed human ApoE4 in different cell types in the brain, using four distinct gene promoter constructs. Many transgenic mice expressing ApoE4 in neurons developed motor problems accompanied by muscle wasting, loss of body weight, and premature death Overexpression of human ApoE4 in neurons resulted in hyperphosphorylation of the microtubule-associated protein tau. In three independent transgenic lines from two different promoter constructs, increased phosphorylation of protein tau was correlated with ApoE4 expression levels. Hyperphosphorylation of protein tau increased with age. In the hippocampus, astrogliosis and ubiquitin-positive inclusions were demonstrated. These findings demonstrate that expression of ApoE in neurons results in hyperphosphorylation of protein tau and suggests a role for ApoE in neuronal cytoskeletal stability and metabolism.
Keywords
E EPSILON-4 ALLELE, CENTRAL-NERVOUS-SYSTEM, ASTROCYTE-SPECIFIC EXPRESSION, DEVELOPING ALZHEIMERS-DISEASE, ISOFORM-SPECIFIC INTERACTIONS, THROMBIN-CLEAVAGE FRAGMENT, AMYLOID PRECURSOR PROTEIN, RECEPTOR-RELATED PROTEIN, E MESSENGER-RNA, NEURITE OUTGROWTH

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Chicago
Tesseur, Ina, Jo Van Dorpe, Kurt Spittaels, Chris Van den Haute, Dieder Moechars, and Fred Van Leuven. 2000. “Expression of Human Apolipoprotein E4 in Neurons Causes Hyperphosphorylation of Protein Tau in the Brains of Transgenic Mice.” American Journal of Pathology 156 (3): 951–964.
APA
Tesseur, I., Van Dorpe, J., Spittaels, K., Van den Haute, C., Moechars, D., & Van Leuven, F. (2000). Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice. AMERICAN JOURNAL OF PATHOLOGY, 156(3), 951–964.
Vancouver
1.
Tesseur I, Van Dorpe J, Spittaels K, Van den Haute C, Moechars D, Van Leuven F. Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice. AMERICAN JOURNAL OF PATHOLOGY. 2000;156(3):951–64.
MLA
Tesseur, Ina, Jo Van Dorpe, Kurt Spittaels, et al. “Expression of Human Apolipoprotein E4 in Neurons Causes Hyperphosphorylation of Protein Tau in the Brains of Transgenic Mice.” AMERICAN JOURNAL OF PATHOLOGY 156.3 (2000): 951–964. Print.
@article{5940794,
  abstract     = {Epidemiological studies have established that the epsilon 4 allele of the ApoE gene (ApoE4) constitutes an important risk factor for Alzheimer's disease and might influence the outcome of central nervous system injury. The mechanism by which ApoE4 contributes to the development of neurodegeneration remains unknown. To test one hypothesis or mode of action of ApoE, we generated transgenic mice that overexpressed human ApoE4 in different cell types in the brain, using four distinct gene promoter constructs. Many transgenic mice expressing ApoE4 in neurons developed motor problems accompanied by muscle wasting, loss of body weight, and premature death Overexpression of human ApoE4 in neurons resulted in hyperphosphorylation of the microtubule-associated protein tau. In three independent transgenic lines from two different promoter constructs, increased phosphorylation of protein tau was correlated with ApoE4 expression levels. Hyperphosphorylation of protein tau increased with age. In the hippocampus, astrogliosis and ubiquitin-positive inclusions were demonstrated. These findings demonstrate that expression of ApoE in neurons results in hyperphosphorylation of protein tau and suggests a role for ApoE in neuronal cytoskeletal stability and metabolism.},
  author       = {Tesseur, Ina and Van Dorpe, Jo and Spittaels, Kurt and Van den Haute, Chris and Moechars, Dieder and Van Leuven, Fred},
  issn         = {0002-9440},
  journal      = {AMERICAN JOURNAL OF PATHOLOGY},
  language     = {eng},
  number       = {3},
  pages        = {951--964},
  title        = {Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice},
  url          = {http://dx.doi.org/10.1016/S0002-9440(10)64963-2},
  volume       = {156},
  year         = {2000},
}

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