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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 810981, 9 pages
http://dx.doi.org/10.4061/2011/810981
Review Article

Introducing Human APOE into Aβ Transgenic Mouse Models

1Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL 60612, USA
2Translational Neurobiology, Medtronic Incorporated, Minneapolis, MN 55432, USA

Received 21 July 2011; Accepted 15 August 2011

Academic Editor: Patrizia Mecocci

Copyright © 2011 Leon M. Tai et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. J. Hardy, “The amyloid hypothesis for Alzheimer's disease: a critical reappraisal,” Journal of Neurochemistry, vol. 110, no. 4, pp. 1129–1134, 2009. View at Publisher · View at Google Scholar
  2. T. Wisniewski and E. M. Sigurdsson, “Murine models of Alzheimer's disease and their use in developing immunotherapies,” Biochimica et Biophysica Acta, vol. 1802, no. 10, pp. 847–859, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. M. Takeda, R. Martínez, T. Kudo et al., “Apolipoprotein e and central nervous system disorders: reviews of clinical findings,” Psychiatry and Clinical Neurosciences, vol. 64, no. 6, pp. 592–607, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. P. B. Verghese, J. M. Castellano, and D. M. Holtzman, “Apolipoprotein E in Alzheimer's disease and other neurological disorders,” The Lancet Neurology, vol. 10, no. 3, pp. 241–252, 2011. View at Publisher · View at Google Scholar
  5. G. Bu, “Apolipoprotein e and its receptors in Alzheimer's disease: pathways, pathogenesis and therapy,” Nature Reviews Neuroscience, vol. 10, no. 5, pp. 333–344, 2009. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Hardy, “Alzheimer's disease: the amyloid cascade hypothesis—an update and reappraisal,” Journal of Alzheimer's Disease, vol. 9, no. 3, supplement, pp. 151–153, 2006. View at Google Scholar · View at Scopus
  7. P. A. Adlard and J. C. Vickers, “Morphologically distinct plaque types differentially affect dendritic structure and organisation in the early and late states of Alzheimer's disease,” Acta Neuropathologica, vol. 103, no. 4, pp. 377–383, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. T. van Groen, L. Liu, S. Ikonen, and I. Kadish, “Diffuse amyloid deposition, but not plaque number, is reduced in amyloid precursor protein/presenilin 1 double-transgenic mice by pathway lesions,” Neuroscience, vol. 119, no. 4, pp. 1185–1197, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. D. R. Thal, E. Capetillo-Zarate, K. Del Tredici, and H. Braak, “The development of amyloid beta protein deposits in the aged brain,” Science of Aging Knowledge Environment, vol. 2006, no. 6, p. re1, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. J. C. Fiala, “Mechanisms of amyloid plaque pathogenesis,” Acta Neuropathologica, vol. 114, no. 6, pp. 551–571, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. D. R. Thal, W. S. T. Griffin, and H. Braak, “Parenchymal and vascular Aβ-deposition and its effects on the degeneration of neurons and cognition in Alzheimer's disease,” Journal of Cellular and Molecular Medicine, vol. 12, no. 5, pp. 1848–1862, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. T. C. Dickson and J. C. Vickers, “The morphological phenotype of β-amyloid plaques and associated neuritic changes in Alzheimer's disease,” Neuroscience, vol. 105, no. 1, pp. 99–107, 2001. View at Publisher · View at Google Scholar · View at Scopus
  13. Q. Xu, A. Bernardo, D. Walker, T. Kanegawa, R. W. Mahley, and Y. Huang, “Profile and regulation of apolipoprotein E (ApoE) expression in the CNS in mice with targeting of green fluorescent protein gene to the ApoE locus,” Journal of Neuroscience, vol. 26, no. 19, pp. 4985–4994, 2006. View at Publisher · View at Google Scholar · View at Scopus
  14. J. Kim, J. M. Basak, and D. M. Holtzman, “The role of apolipoprotein E in Alzheimer's disease,” Neuron, vol. 63, no. 3, pp. 287–303, 2009. View at Publisher · View at Google Scholar · View at Scopus
  15. J. Raber, D. Wong, M. Buttini et al., “Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: increased susceptibility of females,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 18, pp. 10914–10919, 1998. View at Publisher · View at Google Scholar · View at Scopus
  16. I. Gordon, E. Grauer, I. Genis, E. Sehayek, and D. M. Michaelson, “Memory deficits and cholinergic impairments in apolipoprotein E-deficient mice,” Neuroscience Letters, vol. 199, no. 1, pp. 1–4, 1995. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. Ji, Y. Gong, W. Gan, T. Beach, D. M. Holtzman, and T. Wisniewski, “Apolipoprotein E isoform-specific regulation of dendritic spine morphology in apolipoprotein E transgenic mice and Alzheimer's disease patients,” Neuroscience, vol. 122, no. 2, pp. 305–315, 2003. View at Publisher · View at Google Scholar · View at Scopus
  18. R. C. Klein, B. E. Mace, S. D. Moore, and P. M. Sullivan, “Progressive loss of synaptic integrity in human apolipoprotein E4 targeted replacement mice and attenuation by apolipoprotein E2,” Neuroscience, vol. 171, no. 4, pp. 1265–1272, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. J. A. Piedrahita, S. H. Zhang, J. R. Hagaman, P. M. Oliver, and N. Maeda, “Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 89, no. 10, pp. 4471–4475, 1992. View at Publisher · View at Google Scholar · View at Scopus
  20. I. Veinbergs, M. Mante, M. W. Jung, E. Van Uden, and E. Masliah, “Synaptotagmin and synaptic transmission alterations in apolipoprotein E- deficient mice,” Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 23, no. 3, pp. 519–531, 1999. View at Publisher · View at Google Scholar · View at Scopus
  21. J. Robertson, J. Curley, J. Kaye, J. Quinn, T. Pfankuch, and J. Raber, “apoE isoforms and measures of anxiety in probable AD patients and apoE/ mice,” Neurobiology of Aging, vol. 26, no. 5, pp. 637–643, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. Y. Sun, S. Wu, G. Bu et al., “Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte- secreted apoE3 and apoE4 lipoproteins,” Journal of Neuroscience, vol. 18, no. 9, pp. 3261–3272, 1998. View at Google Scholar · View at Scopus
  23. R. E. Hartman, D. F. Wozniak, A. Nardi, J. W. Olney, L. Sartorius, and D. M. Holtzman, “Behavioral phenotyping of GFAP-ApoE3 and -ApoE4 transgenic mice: ApoE4 mice show profound working memory impairments in the absence of Alzheimer's-like neuropathology,” Experimental Neurology, vol. 170, no. 2, pp. 326–344, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. P. van Meer, S. Acevedo, and J. Raber, “Impairments in spatial memory retention of GFAP-apoE4 female mice,” Behavioural Brain Research, vol. 176, no. 2, pp. 372–375, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Buttini, M. Orth, S. Bellosta et al., “Expression of human apolipoprotein E3 or E4 in the brains of apoE/ mice: isoform-specific effects on neurodegeneration,” Journal of Neuroscience, vol. 19, no. 12, pp. 4867–4880, 1999. View at Google Scholar · View at Scopus
  26. M. Buttini, G. Q. Yu, K. Shockley et al., “Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid β peptides but not on plaque formation,” Journal of Neuroscience, vol. 22, no. 24, pp. 10539–10548, 2002. View at Google Scholar · View at Scopus
  27. F. M. Harris, W. J. Brecht, Q. Xu, R. W. Mahley, and Y. Huang, “Increased tau phosphorylation in apolipoprotein E4 transgenic mice is associated with activation of extracellular signal-regulated kinase. Modulation by zinc,” The Journal of Biological Chemistry, vol. 279, no. 43, pp. 44795–44801, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. P. M. Sullivan, B. Han, F. Liu et al., “Reduced levels of human apoE4 protein in an animal model of cognitive impairment,” Neurobiology of Aging, vol. 32, no. 5, pp. 791–801, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. P. M. Sullivan, B. E. Mace, J. C. Estrada, D. E. Schmechel, and M. J. Alberts, “Human Apolipoprotein E4 Targeted Replacement Mice Show Increased Prevalence of Intracerebral Hemorrhage Associated with Vascular Amyloid Deposition,” Journal of Stroke and Cerebrovascular Diseases, vol. 17, no. 5, pp. 303–311, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. K. R. Bales, F. Liu, S. Wu et al., “Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice,” Journal of Neuroscience, vol. 29, no. 21, pp. 6771–6779, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Bour, J. Grootendorst, E. Vogel et al., “Middle-aged human apoE4 targeted-replacement mice show retention deficits on a wide range of spatial memory tasks,” Behavioural Brain Research, vol. 193, no. 2, pp. 174–182, 2008. View at Publisher · View at Google Scholar · View at Scopus
  32. J. Grootendorst, A. Bour, E. Vogel et al., “Human apoE targeted replacement mouse lines: H-apoE4 and h-apoE3 mice differ on spatial memory performance and avoidance behavior,” Behavioural Brain Research, vol. 159, no. 1, pp. 1–14, 2005. View at Publisher · View at Google Scholar · View at Scopus
  33. S. B. Dumanis, J. A. Tesoriero, L. W. Babus et al., “ApoE4 decreases spine density and dendritic complexity in cortical neurons in vivo,” Journal of Neuroscience, vol. 29, no. 48, pp. 15317–15322, 2009. View at Publisher · View at Google Scholar · View at Scopus
  34. B. L. Trommer, C. Shah, S. H. Yun et al., “ApoE isoform affects LTP in human targeted replacement mice,” NeuroReport, vol. 15, no. 17, pp. 2655–2658, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. J. A. Siegel, G. E. Haley, and J. Raber, “Apolipoprotein E isoform-dependent effects on anxiety and cognition in female TR mice,” Neurobiology of Aging. In press. View at Publisher · View at Google Scholar
  36. D. Games, D. Adams, R. Alessandrini et al., “Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein,” Nature, vol. 373, no. 6514, pp. 523–527, 1995. View at Google Scholar · View at Scopus
  37. K. Johnson-Wood, M. Lee, R. Motter et al., “Amyloid precursor protein processing and Aβ42 deposition in a transgenic mouse model of Alzheimer disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 4, pp. 1550–1555, 1997. View at Google Scholar · View at Scopus
  38. M. C. Irizarry, F. Soriano, M. McNamara et al., “Aβ deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse,” Journal of Neuroscience, vol. 17, no. 18, pp. 7053–7059, 1997. View at Google Scholar · View at Scopus
  39. J. C. Dodart, C. Mathis, J. Saura, K. R. Bales, S. M. Paul, and A. Ungerer, “Neuroanatomical abnormalities in behaviorally characterized APP(V717F) transgenic mice,” Neurobiology of Disease, vol. 7, no. 2, pp. 71–85, 2000. View at Publisher · View at Google Scholar · View at Scopus
  40. K. R. Bales, T. Verina, D. J. Cummins et al., “Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 26, pp. 15233–15238, 1999. View at Publisher · View at Google Scholar · View at Scopus
  41. A. M. Fagan, M. Watson, M. Parsadanian, K. R. Bales, S. M. Paul, and D. M. Holtzman, “Human and murine apoE markedly alters Aβ metabolism before and after plaque formation in a mouse model of Alzheimer's Disease,” Neurobiology of Disease, vol. 9, no. 3, pp. 305–318, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. D. M. Holtzman, K. R. Bales, T. Tenkova et al., “Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 97, no. 6, pp. 2892–2897, 2000. View at Publisher · View at Google Scholar · View at Scopus
  43. K. R. Bales, F. Liu, S. Wu et al., “Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice,” Journal of Neuroscience, vol. 29, no. 21, pp. 6771–6779, 2009. View at Publisher · View at Google Scholar · View at Scopus
  44. K. Hsiao, P. Chapman, S. Nilsen et al., “Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice,” Science, vol. 274, no. 5284, pp. 99–102, 1996. View at Publisher · View at Google Scholar · View at Scopus
  45. M. C. Irizarry, M. McNamara, K. Fedorchak, K. Hsiao, and B. T. Hyman, “APP(Sw) transgenic mice develop age-related Aβ deposits and neuropil abnormalities, but no neuronal loss in CA1,” Journal of Neuropathology and Experimental Neurology, vol. 56, no. 9, pp. 965–973, 1997. View at Google Scholar · View at Scopus
  46. R. H. Takahashi, T. A. Milner, F. Li et al., “Intraneuronal Alzheimer Aβ42 accumulates in multivesicular bodies and is associated with synaptic pathology,” American Journal of Pathology, vol. 161, no. 5, pp. 1869–1879, 2002. View at Google Scholar · View at Scopus
  47. J. D. Fryer, K. Simmons, M. Parsadanian et al., “Human apolipoprotein E4 alters the amyloid-β 40:42 ratio and promotes the formation of cerebral amyloid angiopathy in an amyloid precursor protein transgenic model,” Journal of Neuroscience, vol. 25, no. 11, pp. 2803–2810, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. A. Y. Hsia, E. Masliah, L. Mcconlogue et al., “Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 6, pp. 3228–3233, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. H. Oakley, S. L. Cole, S. Logan et al., “Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation,” Journal of Neuroscience, vol. 26, no. 40, pp. 10129–10140, 2006. View at Publisher · View at Google Scholar · View at Scopus
  50. K. Youmans, K. Laxton, L. M. Jungbauer, C. Yu, and M. LaDu, The Effects of Human ApoE on Amyloid-beta Pathology in a Novel Transgenic Mouse Model, Society for Neuroscience, San Diego, Calif, USA, 2010.
  51. K. Youmans, L. Tai, K. Laxton et al., “ApoE isoform-specific effects on Aß pathology in EFAD mice,” in Proceedings of the 2nd annual symposium of ApoE, ApoE Receptors, and Neurodegeneration, Chicago, Ill, USA, 2011.
  52. K. L. Youmans, “The effects of human apoE on amyloid-beta (42) pathology and synaptic loss in a novel transgenic mouse model,” in Proceedings of the American Society for Neurochemistry Meeting, Transactions of the American Society for Neurochemistry, Santa Fe, NM, USA, 2010.
  53. C. Yu, K. L. Youmans, L. M. Jungbauer et al., “Selective increases in soluble ApoE4 and Aß42 in EFAD mouse brains,” in Proceedings of the ApoE, ApoE Receptors and Neurodegeneration, Chicago, Ill, USA, 2011.
  54. D. M. Hatters, C. A. Peters-Libeu, and K. H. Weisgraber, “Apolipoprotein E structure: insights into function,” Trends in Biochemical Sciences, vol. 31, no. 8, pp. 445–454, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. I. Tesseur, J. Van Dorpe, K. Bruynseels et al., “Prominent axonopathy and disruption of axonal transport in transgenic mice expressing human apolipoprotein E4 in neurons of brain and spinal cord,” American Journal of Pathology, vol. 157, no. 5, pp. 1495–1510, 2000. View at Google Scholar · View at Scopus
  56. J. D. Smith, J. Sikes, and J. A. Levin, “Human apolipoprotein E allele-specific brain expressing transgenic mice,” Neurobiology of Aging, vol. 19, no. 5, pp. 407–413, 1998. View at Publisher · View at Google Scholar · View at Scopus
  57. G. Huber, W. März, J. R. Martin et al., “Characterization of transgenic mice expressing Apolipoprotein E4(C112R) and Apolipoprotein E4(L28P; C112R),” Neuroscience, vol. 101, no. 1, pp. 211–218, 2000. View at Publisher · View at Google Scholar · View at Scopus
  58. B. H. Bowman, L. Jansen, F. Yang et al., “Discovery of a brain promoter from the human transferrin gene and its utilization for development of transgenic mice that express human apolipoprotein E alleles,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 26, pp. 12115–12119, 1995. View at Publisher · View at Google Scholar · View at Scopus
  59. I. Tesseur, J. Van Dorpe, K. Spittaels, C. Van den Haute, D. Moechars, and F. Van Leuven, “Expression of human apolipoprotein E4 in neurons causes hyperphosphorylation of protein tau in the brains of transgenic mice,” American Journal of Pathology, vol. 156, no. 3, pp. 951–964, 2000. View at Google Scholar · View at Scopus
  60. S. H. Han, G. Einstein, K. H. Weisgraber et al., “Apolipoprotein E is localized to the cytoplasm of human cortical neurons: a light and electron microscopic study,” Journal of Neuropathology and Experimental Neurology, vol. 53, no. 5, pp. 535–544, 1994. View at Google Scholar · View at Scopus
  61. S. H. Han, C. Hulette, A. M. Saunders et al., “Apolipoprotein E is present in hippocampal neurons without neurofibrillary tangles in Alzheimer's disease and in age-matched controls,” Experimental Neurology, vol. 128, no. 1, pp. 13–26, 1994. View at Publisher · View at Google Scholar · View at Scopus
  62. M. Buttini, E. Masliah, G. Q. Yu et al., “Cellular source of apolipoprotein E4 determines neuronal susceptibility to excitotoxic injury in transgenic mice,” American Journal of Pathology, vol. 177, no. 2, pp. 563–569, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. H. K. Chen, Z. S. Ji, S. E. Dodson et al., “Apolipoprotein E4 domain interaction mediates detrimental effects on mitochondria and is a potential therapeutic target for alzheimer disease,” The Journal of Biological Chemistry, vol. 286, no. 7, pp. 5215–5221, 2011. View at Publisher · View at Google Scholar
  64. E. J. Mufson, W. C. Benzing, G. M. Cole et al., “Apolipoprotein E-immunoreactivity in aged rhesus monkey cortex: colocalization with amyloid plaques,” Neurobiology of Aging, vol. 15, no. 5, pp. 621–628, 1994. View at Publisher · View at Google Scholar · View at Scopus
  65. S. C. Fujita, K. Sakuta, R. Tsuchiya, and H. Hamanaka, “Apolipoprotein E is found in astrocytes but not in microglia in the normal mouse brain,” Neuroscience Research, vol. 35, no. 2, pp. 123–133, 1999. View at Publisher · View at Google Scholar · View at Scopus
  66. D. J. Stone, I. Rozovsky, T. E. Morgan, C. P. Anderson, H. Hajian, and C. E. Finch, “Astrocytes and microglia respond to estrogen with increased apoE mRNA in vivo and in vitro,” Experimental Neurology, vol. 143, no. 2, pp. 313–318, 1997. View at Publisher · View at Google Scholar · View at Scopus
  67. S. Grehan, E. Tse, and J. M. Taylor, “Two distal downstream enhancers direct expression of the human apolipoprotein E gene to astrocytes in the brain,” Journal of Neuroscience, vol. 21, no. 3, pp. 812–822, 2001. View at Google Scholar · View at Scopus
  68. J. Poirier, “Apolipoprotein E, cholesterol transport and synthesis in sporadic Alzheimer's disease,” Neurobiology of Aging, vol. 26, no. 3, pp. 355–361, 2005. View at Publisher · View at Google Scholar · View at Scopus
  69. J. Poirier, “Apolipoprotein E represents a potent gene-based therapeutic target for the treatment of sporadic Alzheimer's disease,” Alzheimer's and Dementia, vol. 4, no. 1, supplement, pp. S91–S97, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. G. Ramaswamy, Q. Xu, Y. Huang, and K. H. Weisgraber, “Effect of domain interaction on apolipoprotein E levels in mouse brain,” Journal of Neuroscience, vol. 25, no. 46, pp. 10658–10663, 2005. View at Publisher · View at Google Scholar · View at Scopus
  71. R. L. Raffaï, L. M. Dong, R. V. Farese, and K. H. Weisgraber, “Introduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 20, pp. 11587–11591, 2001. View at Publisher · View at Google Scholar · View at Scopus
  72. P. Bertrand, J. Poirier, T. Oda, C. E. Finch, and G. M. Pasinetti, “Association of apolipoprotein E genotype with brain levels of apolipoprotein E and apolipoprotein J (clusterin) in Alzheimer disease,” Molecular Brain Research, vol. 33, no. 1, pp. 174–178, 1995. View at Publisher · View at Google Scholar · View at Scopus
  73. F. Glöckner, V. Meske, and T. G. Ohm, “Genotype-related differences of hippocampal apolipoprotein E levels only in early stages of neuropathological changes in Alzheimer's disease,” Neuroscience, vol. 114, no. 4, pp. 1103–1114, 2002. View at Publisher · View at Google Scholar · View at Scopus
  74. Y. Sun, S. Wu, G. Bu et al., “Glial fibrillary acidic protein-apolipoprotein E (apoE) transgenic mice: astrocyte-specific expression and differing biological effects of astrocyte- secreted apoE3 and apoE4 lipoproteins,” Journal of Neuroscience, vol. 18, no. 9, pp. 3261–3272, 1998. View at Google Scholar · View at Scopus
  75. K. F. Tang, L. Cai, and J. N. Zhou, “Observation of the density and size of cells in hippocampus and vascular lesion in thalamus of GFAP-apoE transgenic mice,” Neuroscience Bulletin, vol. 25, no. 4, pp. 167–178, 2009. View at Publisher · View at Google Scholar · View at Scopus
  76. O. Wirths and T. A. Bayer, “Neuron loss in transgenic mouse models of Alzheimer's disease,” International Journal of Alzheimer's Disease, vol. 2010, Article ID 723782, 6 pages, 2010. View at Publisher · View at Google Scholar · View at Scopus
  77. J. C. Dodart, K. R. Bales, E. M. Johnstone, S. P. Little, and S. M. Paul, “Apolipoprotein E alters the processing of the β-amyloid precursor protein in APPV717F transgenic mice,” Brain Research, vol. 955, no. 1-2, pp. 191–199, 2002. View at Publisher · View at Google Scholar · View at Scopus
  78. K. R. Bales, T. Verina, D. J. Cummins et al., “Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease,” Proceedings of the National Academy of Sciences of the United States of America, vol. 96, no. 26, pp. 15233–15238, 1999. View at Publisher · View at Google Scholar · View at Scopus
  79. K. R. Bales, T. Verina, R. C. Dodel et al., “Lack of apolipoprotein E dramatically reduces amyloid beta-peptide deposition,” Nature genetics, vol. 17, no. 3, pp. 263–264, 1997. View at Google Scholar · View at Scopus
  80. D. M. Holtzman, A. M. Fagan, B. Mackey et al., “Apolipoprotein E facilitates neuritic and cerebrovascular plaque formation in an Alzheimer's disease model,” Annals of Neurology, vol. 47, no. 6, pp. 739–747, 2000. View at Google Scholar · View at Scopus
  81. J. Raber, D. Wong, G. Q. Yu et al., “Apolipoprotein E and cognitive performance,” Nature, vol. 404, no. 6776, pp. 352–354, 2000. View at Google Scholar · View at Scopus
  82. R. E. Hartman, H. Laurer, L. Longhi et al., “Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer's disease,” Journal of Neuroscience, vol. 22, no. 23, pp. 10083–10087, 2002. View at Google Scholar · View at Scopus
  83. C. A. Colton, D. M. Wilcock, D. A. Wink, J. Davis, W. E. Van Nostrand, and M. P. Vitek, “The effects of NOS2 gene deletion on mice expressing mutated human AβPP,” Journal of Alzheimer's Disease, vol. 15, no. 4, pp. 571–587, 2008. View at Google Scholar · View at Scopus
  84. H. Belinson, D. Lev, E. Masliah, and D. M. Michaelson, “Activation of the amyloid cascade in apolipoprotein E4 transgenic mice induces lysosomal activation and neurodegeneration resulting in marked cognitive deficits,” Journal of Neuroscience, vol. 28, no. 18, pp. 4690–4701, 2008. View at Publisher · View at Google Scholar · View at Scopus
  85. I. Dolev and D. M. Michaelson, “A nontransgenic mouse model shows inducible amyloid-β (Aβ) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 38, pp. 13909–13914, 2004. View at Publisher · View at Google Scholar · View at Scopus
  86. S. Oddo, A. Caccamo, J. D. Shepherd et al., “Triple-transgenic model of Alzheimer's Disease with plaques and tangles: intracellular Aβ and synaptic dysfunction,” Neuron, vol. 39, no. 3, pp. 409–421, 2003. View at Publisher · View at Google Scholar · View at Scopus
  87. S. Oddo, A. Caccamo, I. F. Smith, K. N. Green, and F. M. LaFerla, “A dynamic relationship between intracellular and extracellular pools of Aβ,” American Journal of Pathology, vol. 168, no. 1, pp. 184–194, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. C. Casas, N. Sergeant, J. M. Itier et al., “Massive CA1/2 neuronal loss with intraneuronal and N-terminal truncated Aβ42 accumulation in a novel Alzheimer transgenic model,” American Journal of Pathology, vol. 165, no. 4, pp. 1289–1300, 2004. View at Google Scholar · View at Scopus
  89. R. Radde, T. Bolmont, S. A. Kaeser et al., “Aβ42-driven cerebral amyloidosis in transgenic mice reveals early and robust pathology,” EMBO Reports, vol. 7, no. 9, pp. 940–946, 2006. View at Publisher · View at Google Scholar · View at Scopus
  90. M. A. Chishti, D. S. Yang, C. Janus et al., “Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695,” The Journal of Biological Chemistry, vol. 276, no. 24, pp. 21562–21570, 2001. View at Publisher · View at Google Scholar · View at Scopus