Does my mouse have Alzheimer's disease?

Genes, Brain and Behavior

Volumn 1, Issue 3, 2002, Pages 142-155

  Dodart, J C ^a   Mathis, C ^b   Bales, K R ^a   Paul, S M ^a  

^a ELI LILLY AND COMPANY   (United States)

^b CNRS   (France)

Author keywords

A ; Alzheimer's disease; Amyloid; APP; Behavior; Learning and memory; Neuropathology; Transgenic mouse models

Indexed keywords

AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN;

ALZHEIMER DISEASE; ANIMAL BEHAVIOR; ANIMAL MODEL; BEHAVIOR; COGNITIVE DEFECT; DEGENERATIVE DISEASE; GLIOSIS; LEARNING; MAZE TEST; MEMORY; MEMORY DISORDER; MOUSE; MOUSE STRAIN; NEUROLOGIC DISEASE; NEUROPATHOLOGY; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; REVIEW; SENILE PLAQUE; SPATIAL MEMORY; SYNAPSE; TRANSGENIC MOUSE; WORKING MEMORY;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANIMALS; BEHAVIOR, ANIMAL; BRAIN; DISEASE MODELS, ANIMAL; HUMANS; MICE; MICE, TRANSGENIC; MODELS, GENETIC; PHENOTYPE;

ANIMALIA; MUS MUSCULUS;

EID: 0038460177     PISSN: 16011848     EISSN: None     Source Type: Journal    
DOI: 10.1034/j.1601-183X.2002.10302.x     Document Type: Review

References (125)

1. Albert, M.S. (1996) Cognitive and neurobiologic markers of early Alzheimer disease. Proc Natl Acad Sci USA 93, 13547-13551.
2. Almkvist, O. (1996) Neuropsychological features of early ease: preclinical and clinical stages. Acta Neurol Scandsupplement 165, 63-71.
3. Andrä, K., Abramowski, D., Duke, M., Probst, A., Wiederhold, K.H., Burki, K., Goedert, M., Sommer, B. & Staufenbiel, M. (1996) Expression of APP in transgenic mice: a comparison of neuron-specific promoters. Neurobiol Aging 17, 183-190.
4. Apelt, J. & Schliebs, R. (2001) β-amyloid-induced glial expression of both pro- and anti-inflammatory cytokines in cerebral cortex of aged transgenic Tg2576 mice with Alzheimer plaque pathology. Brain Res 894, 21-30
5. V717F transgenic mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 96, 15233-15238.
6. Bales, K.R., Verina, T. Du Dodel, R.C.Y. Altstiel, L., Bender, M., Hyslop, P., Johnstone, E.M., Little, S.P., Cummins, D.J., Piccardo, P., Ghetti, B. & Paul, S.M. (1997) Lack of apolipoprotein E dramatically reduces amyloid β-peptide deposition. Nat Genet 17, 263-264.
7. Bard, F., Cannon, C., Barbour, R., Burke, R.L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Lieberburg, I., Motter, R., Nguyen, M., Soriano, F., Vasquez, N., Weiss, K., Welch, B., Seubert, P., Schenk, D. & Yednock, T. (2000) Peripherally administered antibodies against amyloid β-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat Med 6, 916-919.
8. Bayer, T.A., Wirth, O., Majtenyi, K., Hartmann, T., Multhaup, G., Beyreuther, K. & Czech, C. (2001) Key factors in Alzheimer's disease: β-amyloid precursor protein processing, metabolism and intraneuronal transport. Brain Pathol 11, 1-11
9. Benzing, W.C., Wujek, J.R., Ward, E.K., Shaffer, D., Ashe, K.H., Younkin, S.G. & Brunden, K.R. (1999) Evidence for glial-mediated inflammation in aged APPsw transgenic mice. Neurobiol Aging 20, 581-589.
10. Berger-Sweeney, J., McPhie, D.L. Arters, J.A., Greenan, J., Oster-Granite, M.L. & Neve, R.L. (1999) Impairments in learning and memory accompanied by neurodegeneration in mice transgenic for the carboxylterminus of the amyloid precursor protein. Mol Brain Res 66, 150-162.
11. Bondolfi, L., Calhoun, M., Ermini, F., Kuhn, H.G., Wiederhold, K.H., Walker, L., Staufenbiel, M. & Jucker, M. (2002) Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J Neurosci 22, 515-522.
12. Borchelt, D.R., Ratovitski, T., van Lare, J., Lee, M.K., Gonzales, V., Jenkins, N.A., Copeland, N.G., Price, D.L. & Sisodia, S.S. (1997) Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins. Neuron 19, 939-945.
13. Borchelt, D.R., Thinakaran, G., Eckman, C.B., Lee, M.K., Davenport, F., Ratovitsky, T., Prada, C.M., Kim, G., Seekins, S., Yager, D., Slunt, H.H., Wang, R., Seeger, M., Levey, A.I., Gandy, S.E., Copeland, N.G., Jenkins, N.A., Price, D.L., Younkin, S.G. & Sisodia, S.S. (1996) Familial Alzheimer's disease-linked presenilin 1 variants elevate Aβ1-42/1-40 ratio in vitro and in vivo. Neuron 17, 1005-1013.
14. Bornemann, K.D., Wiederhold, K.H., Pauli, C., Ermini, F., Stalder, M., Schnell, L., Sommer, B., Jucker, M. & Staufenbiel, M. (2001) Aβ-induced inflammatory processes in microglia cells of APP23 transgenic mice. Am J Pathol 158, 63-73.
15. Buxbaum, J.D., Christensen, J.L., Ruefli, A.A., Greengard, P. & Loring, J.F. (1993) Expression of APP in brains of transgenic mice containing the entire human APP gene. Biochem Biophys Res Commun 197, 639-645.
16. Calhoun, M.E., Burgermeister, P., Phinney, A.L., Stalder, M., Tolnay, M., Wiederhold, K.H., Abramowski, D., Sturchler-Pierrat, C., Sommer, B., Staufenbiel, M. & Jucker, M. (1999) Neuronal overexpression of mutant amyloid precurscr protein results in prominent deposition of cerebrovascular amyloid. Proc Natl Acad Sci U S A 96, 14088-14093.
17. Calhoun, M.E., Wiederhold, K.H., Abramowski, D., Phinney, A.L., Probst, A., Sturchler-Pierrat, C., Staufenbiel, M., Sommer, B. & Jucker, M. (1998) Neuron loss in APP transgenic mice. Nature 395, 755-756.
18. Carlson, G.A., Borchelt, D.R., Dake, A., Turner, S., Danielson, V., Coffin, J.D., Eckman, C., Meiners, J., Nilsen, S.P., Younkin, S.G. & Hsiao, K.K. (1997) Genetic modification of the phenotypes produced by amyloid precursor protein overexpression in transgenic mice. Hum Mol Genet 6, 1951-1959.
19. Chapman, P.F., Falinska, A.M., Knevett, S.G. & Ramsay, M.F. (2001) Genes, models and Alzheimer's disease. Trends Genet 17, 254-261.
20. Chapman, P.F., White, G.L., Jones, M.W., Cooper-Blacketer, D. Marshall, V.J., Irizarry, M., Younkin, L., Good, M.A., Bliss, T.V., Hyman, B.T., Younkin, S.G. & Hsiao, K.K. (1999) Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice. Nat Neurosci 2, 271-276.
21. Chen, G., Chen, K.S., Knox, J., Inglis, J., Bernard, A., Martin, S.J., Justice, A., McConlogue, L., Games, D., Freedman, S.B. & Morris, R.G.M. (2000) A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease. Nature 408, 975-979.
22. Cherny, R.A., Atwood, C.S., Xilinas, M.E., Gray, D.N., Jones, W.D., McLean, C.A., Barnham, K.J., Volitakis, I., Fraser, F.W., Kim, Y., Huang, X., Goldstein, L.E., Moir, R.D., Lim, J.T., Beyreuther, K., Zheng, H., Tanzi, R.E., Masters, C.L. & Bush, A.I. (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30, 665-676.
23. Chishti, M.A., Yang, D.S., Janus, C., Phinney, A.L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., Turner, S., Lozza, G., Grilli, M., Kunicki, S., Morissette, C., Paquette, J., Gervais, F., Bergeron, C., Fraser, P.E., Carlson, G.A., George-Hyslop, P.S. & Westaway, D. (2001) Earlyonset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 276, 21562-21570.
24. Chui, D.H., Tanahashi, H., Ozawa, K., Ikeda, S., Checler, F., Ueda, O., Suzuki, H., Araki, W., Inoue, H., Shirotani, K., Takahashi, K., Gallyas, F. & Tabira, T. (1999) Transgenic mice with Alzheimer presenilin 1 mutations show accelerated neurodegeneration without amyloid plaque formation. Nat Med 5, 560-564.
25. Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G. et al. (1997) Mutant presenilins of Alzheimer's disease increase production of 42-residue amyloid β-protein in both transfected cells and transgenic mice Nat Med 3, 67-72.
26. Collie, A. & Maruff, P. (2000) The neuropsychology of preclinical Alzheimer's disease and mild cognitive impairment. Neurosci Biobehav Rev 24, 365-374.
27. Crawley, J.N. (1999) Behavioral phenotyping of transgenic and knockout mice: experimental design and evaluation of general health, sensory functions. motor abilities, and specific behavioral tests. Brain Res 835, 18-26.
28. Crawley, J.N., Belknap, J.K., Collins, A., Crabbe, J.C., Frankel, W., Henderson, N., Hitzemann, R.J., Maxson, S.C., Miner, L.L., Silva, A.J., Wehner, J.M., Wynshaw-Boris, A. & Paylor, R. (1997a) Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies. Psychopharmacology 132, 107-124.
29. Crawley, J.N. & Paylor, R. (1997b) A proposed test battery and constellations of specific behavioral paradigms to investigate the behavioral phenotypes of transgenic and knockout mice. Horm Behav 31, 197-211.
30. Cummings, J.L. (2000) Cognitive and behavioral heterogeneity in Alzheimer's disease: seeking the neurobiological basis. Neurobiol Aging 21, 845-861.
31. Delacourte, A. & Buée, L. (1997) Normal and pathological Tau proteins as factors for microtubule assembly. Int Rev Cytol 171, 167-224.
32. DeMattos, R.B., Bales, K.R., Cummins, D.J., Dodart, J.C., Paul, S.M. & Holtzman, D.M. (2001) Peripheral anti-Aβ antibody alters CNS and plasma Aβ clearance and decreases brain Aβ burden in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 98, 8850-8855.
33. Dickson, D.W. (1997) The pathogenesis of senile plaques. J Neuropathol Exp Neurol 56, 321-339.
34. Dodart, J.C., Bales, K.R., Gannon, K.S., Greene, S.J., DeMattos, R.B., Mathis, C., DeLong, C.A., Wu, S., Wu, X., Holtzman, D.M. & Paul, S.M. (2002) Immunization reverses memory deficits without reducing brain Aβ burden in Alzheimer's disease model. Nat Neurosci 5, 452-457.
35. Dodart, J.C., Mathis, C., Bales, K.R., Paul, S.M. & Ungerer, A. (1999a) Early regional cerebral glucose hypometabolism in transgenic mice overexpressing the V717F β-amyloid precursor protein. Neurosci Lett 277, 49-52.
36. V717F transgenic mice. Neurobiol Dis 7, 71-85.
37. Dodart, J.C., Mathis, C. & Ungerer, A. (1997) Scopolamine-induced deficits in a two-trial object recognition task in mice. Neuroreport 8, 1173-1178.
38. Dodart, J.C., Meziane, H., Mathis, C., Bales, K.R., Paul, S.M. & Ungerer, A (1999b) Behavioral disturbances in transgenic mice overexpressing the V717F β-amyloid precursor protein. Behav Neurosci 113, 982-990.
39. Dovey, H.F., John, V., Anderson, J.P., Chen, L.Z., de Saint Andrieu, P., Fang, L.Y., Freedman, S.B., Folmer, B., Goldbach, E., Holsztynska, E.J., Hu, K.L., Johnson-Wood, K.L., Kennedy, S.L., Kholodenko, D., Knops, J.E., Latimer, L.H., Lee, M., Liao, Z., Lieberburg, I.M., Motter, R.N., Mutter, L.C., Nietz, J., Quinn, K.P., Sacchi, K.L., Seubert, P.A., Shopp, G.M., Thorsett, E.D., Tung, J.S., Wu, J., Yang, S., Yin, C.T., Schenk, D.B., May, P.C., Altstiel, L.D., Bender, M.H., Boggs, L.N., Britton, T.C., Clemens, J.C., Czilli, D.L, Dieckman-McGinty, D.K., Droste, J.J., Fuson, K.S., Gitter, B.D., Hyslop, P.A., Johnstone, E.M., Li, W.Y., Little, S.P., Mabry, T.E., Miller, F.D. & Audia, J.E. (2001) Functional gamma-secretase inhibitors reduce β-amyloid peptide levels in brain. J Neurochem 76, 173-181.
40. Duff, K., Eckman, C. & Zehr, C., Yu X., Prada, C.M., Perez-tur, J., Hutton, M., Buee, L., Harigaya, Y., Yager, D., Morgan, D., Gordon, M.N., Holcomb, L., Refolo, L., Zenk, B., Hardy, J. & Younkin, S. (1996) Increased amyloidβ42 (43) in brains of mice expressing mutant presenilin 1. Nature 383, 710-713.
41. Fagan, A.M., Watson, M., Parsadanian, M., Bales, K.R., Paul, S.M. & Holtzman, D.M. (2002) Human and Murine ApoE Markedly Alters Aβ Metabolism before and after Plaque Formation in a Mouse Model of Alzheimer's Disease. Neurobiol Dis 9, 305-318.
42. Ferris, S.H. & Kluger, A. (1997) Assessing cognition in Alzheimer disease research. Alzheimer Dis Assoc Disord 11, 45-49.
43. V717F transgenic mouse model of Alzheimer's disease. J Neurosci Meth 108, 145-152.
44. Fitzjohn, S.M., Morton, R.A., Kuenzi, F., Rosahl, T.W., Shearman, M., Lewis, H., Smith, D., Reynolds, D.S., Davies, C.H., Collingridge, G.L. & Seabrook, G.R. (2001) Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein. J Neurosci 21, 4691-4698.
45. Fleischman, D.A. & Gabrieli, J. (1999) Long-term memory in Alzheimer's disease. Curr Opin Neurobiol 9, 240-244.
46. Frautschy, S.A., Yang, F., Irrizarry, M., Hyman, B., Saido, T.C., Hsiao, K. & Cole, G.M. (1998) Microglial response to amyloid plaques in APPsw transgenic mice. Am J Pathol 152, 307-317.
47. Gabrieli, J.D.E (1996) Memory systems analyses of mnemonic disorders in aging and age-related diseases. Proc Natl Acad Sci USA 93, 13534-13540.
48. Games, D., Adams, D., Alessandrini, R., Barbour, R., Berthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., Guido, T., Hagopian, S., Johnson-Wood, K., Khan, K., Lee, M., Leibowitz, P., Lieberburg, I., Little, S., Masliah, E., McConlogue, L., Montoya-Zavala, M., Mucke, L., Paganini, L., Penniman, E., Power, M., Schenk, D., Seubert, P., Snyder, B., Soriano, F., Tan, H., Vitale, J., Wadsworth, S., Wolozin, B. & Zhao, J. (1995) Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein. Nature 373, 523-527.
49. Gerlai, R. (2001a) Behavioral tests of hippocampal function: simple paradigms complex problems. Behav Brain Res 125, 269-277.
50. Gerlai, R. (2001b) Gene targeting: technical confounds and potential solutions in behavioral brain research. Behav Brain Res 125, 13-21.
51. Geula, C. (1998) Abnormalities of neural circuitry in Alzheimer's disease: hippocampus and cortical cholinergic innervation. Neurology 51, S18-S29.
52. Giacchino, J., Criado, J.R., Games, D. & Henriksen, S. (2000) In vivo synaptic transmission in young and aged amyloid precursor protein transgenic mice. Brain Res 876, 185-190.
53. Glenner, G.G. & Wong, C.W. (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120, 885-890.
54. Gonzales-Lima, F., Berndt, J.D., Valla, J.E., Games, D. & Reiman, E.M. (2001) Reduced corpus callosum, fornix and hippocampus in PDAPP transgenic mouse model of Alzheimer's disease. Neuroreport 12, 2375-2379.
55. Goodman, Y. & Mattson, M.P. (1994) Secreted forms of β-amyloid precursor protein protect hippocampal neurons against amyloid β-peptide-induced oxidative injury. Exp Neurol 128, 1-12.
56. Götz, J., Chen, F., van Dorpe, J. & Nitsch, R.M. (2001) Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ42 fibrils. Science 293, 1491-1494
57. Hardy, J. (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci 20, 154-159.
58. Higgins, L.S., Holtzman, D.M., Rabin, J., Mobley, W.C. & Cordell, B. (1994) Transgenic mouse brain histopathology resembles early Alzheimer's disease Ann Neurol 35, 598-607.
59. Higgins, L.S., Rodems, J.M., Catalano, R., Quon, D. & Cordell, B. (1995) Early Alzheimer disease-like histopathology increases in frequency with age in mice transgenic for β-APP751. Proc Natl Acad Sci USA 92, 4402-4406
60. Hock, B.J. & Lamb, B.T. (2001) Transgenic mouse models of Alzheimer's disease. Trends Genet 17, S7-S12.
61. Holcomb, L.A., Gordon, M.N., Jantzen, P., Hsiao, K., Duff, K. & Morgan, D. (1999) Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits. Behav Genet 29, 177-185.
62. Holcomb, L., Gordon, M.N. & McGowan, E., Yu X., Benkovic, S., Jantzen, P., Wright, K., Saad, I., Mueller, R., Morgan, D., Sanders, S., Zehr, C., O'Campo, K., Hardy, J., Prada, C.M., Eckman, C., Younkin, S., Hsiao, K. & Duff, K. (1998) Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes. Nat Med 4, 97-100.
63. Holmes, A., Wrenn, C.C., Harris, A.P., Thayer, K.E. & Crawley, J.N. (2002) Behavioral profiles of inbred strains on novel olfactory, spatial and emotional tests for reference memory in mice. Genes, Brain Behav 1, 55-69.
64. Holtzman, D.M., Bales, K.R., Tenkova, T., Fagan, A.M., Parsadanian, M., Sartorius, L.J., Mackey, B., Olney, J., McKeel, D., Wozniak, D. & Paul, S.M. (2000) Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer's disease. Proc Natl Acad Sci USA 97, 2892-2897
65. Holtzman, D.M., Bales, K.R., Wu, S., Bhat, P., Parsadanian, M., Fagan, A.M., Chang, L.K., Sun, Y. & Paul, S.M. (1999) Expression of human apolipoprotein E reduces amyloid-β deposition in a mouse model of Alzheimer's disease. J Clin Invest 103, R15-R21.
66. Hsia, A.Y., Masliah, E. & McConlogue, L., Yu G.Q., Tatsuno, G., Hu, K., Kholodenko, D., Malenka, R.C., Nicoll, R.A. & Mucke L. Plaque-dependent disruption of neural circuits in Alzheimer's disease mouse models. Proc Natl Acad Sci USA 96, 3228-3233.
67. Hsiao, K.K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F. & Cole, G. (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice Science 274, 99-102.
68. Huitron-Resendiz, S., Sanchez-Alavez, M., Gallegos, R., Berg, G., Crawford, E., Giacchino, J.L., Games, D., Henriksen, S.J. & Criado, J.R. (2002) Ageindependent and age-related deficits in visuospatial learning, sleepwake states, thermoregulation and motor activity in PDAPP mice. Brain Res 928, 126-137.
69. Irizarry, M.C., McNamara, M., Fedorchak, K., Hsiao, K. & Hyman, B.T. (1997a) APPSw transgenic mice develop age-related Aβ deposits and neuropil abnormalities, but no neuronal loss in CA1. J Neuropathol Exp Neurol 56, 965-973.
70. Irizarry, M.C., Soriano, F., McNamara, M., Page, K.J., Schenk, D., Games, D. & Hyman, B.T. (1997b) Aβ deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J Neurosci 17, 7053-7059.
71. Jantzen, P.T., Connor, K.E., DiCarlo, G., Wenk, G.L., Wallace, J.L., Rojiani, A.M., Coppola, D., Morgan, D. & Gordon, M.N. (2002) Microglial activation and β-amyloid deposit reduction caused by a nitric oxide-releasing nonsteroidal anti-inflammatory drug in amyloid precursor protein plus presenilin-1 transgenic mice. J Neurosci 22, 2246-2254.
72. Janus, C., Pearson, J., McLaurin, J., Mathews, P.M., Jiang, Y., Schmidt, S.D., Chishti, M.A., Horne, P., Heslin, D., French, J., Mount, H.T., Nixon, RA., Mercken, M., Bergeron, C., Fraser, P.E., St George-Hyslop, P. & Westaway, D. (2000) Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease. Nature 408, 979-982.
73. Janus, C. & Westaway, D. (2001) Transgenic mouse models of Alzheimer's disease. Physiol Behav 73, 873-886
74. Johnson-Wood, K., Lee, M., Motter, R., Hu, K., Gordon, G., Barbour, R., Khan, K., Gordon, M., Tan, H., Games, D., Lieberburg, I., Schenk, D., Seubert, P. & McConlogue, L. (1997) Amyloid precursor protein processing and Aβ42 deposition in a transgenic mouse model of Alzheimer disease Proc Natl Acad Sci USA 94, 1550-1555.
75. Kalback, W., Watson, M.D., Kokjohn, T.A., Kuo, Y.M., Weiss, N., Luehrs D.C., Lopez, J., Brune, D., Sisodia, S.S., Staufenbiel, M., Emmerling, M. & Roher, A.E. (2002) APP transgenic mice Tg2576 accumulate Aβ peptides that are distinct from the chemically modified and insoluble peptides deposited in Alzheimer's disease senile plaques. Biochemistry 41, 922-992
76. Kammesheidt, A., Boyce, F.M., Spanoyannis, A.F., Cummings, B.J., Ortegon, M., Cotman, C., Vaught, J.L. & Neve, R.L. (1992) Deposition of β/A4 immunoreactivity and neuronal pathology in transgenic mice expressing the carboxyl-terminal fragment of the Alzheimer amyloid precursor in the brain. Proc Natl Acad Sci USA 89, 10857-10861.
77. Kawarabayashi, T., Younkin, L.H., Saido, T.C., Shoji, M., Ashe, K.H. & Younkin, S.G. (2001) Age-dependent changes in brain, CSF, and plasma amyloid β protein in the Tg2576 transgenic mouse model of Alzheimer's disease. J Neurosci 21, 372-381.
78. King, D.L. & Arendash, G.W. (2002) Maintained synaptophysin immunoreactivity in Tg2576 transgenic mice during aging: correlations with cognitive impairment. Brain Res 926, 58-68.
79. King, D.L., Arendash, G.W., Crawford, F., Sterk, T., Menendez, J. & Mullan, M.J. (1999) Progressive and gender-dependent cognitive impairment in the APP (SW) transgenic mouse model for Alzheimer's disease. Behav Brain Res 103, 145-162.
80. Koistinaho, M., Ort, M., Cimadevilla, J.M., Vondrous, R., Cordell, B., Koistinaho, J., Bures, J. & Higgins, L.S. (2001) Specific spatial learning deficits become severe with age in β-amyloid precursor protein transgenic mice that harbor diffuse β-amyloid deposits but do not form plaques. Proc Natl Acad Sci USA 98, 14675-14680.
81. Koo, E.H., Park, L. & Selkoe, D.J. (1993) Amyloid β-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth. Proc Natl Acad Sci USA 90, 4748-4752.
82. Kuo, Y.M., Kokjohn, T.A., Beach, T.G., Sue, L.I., Brune, D., Lopez, J.C., Kalback, W.M., Abramowski, D., Sturchler-Pierrat, C., Staufenbiel, M. & Roher, A.E. (2001) Comparative analysis of amyloid-β chemical structure and amyloid plaque morphology of transgenic mouse and Alzheimer's disease brains. J Biol Chem 276, 12991-12998.
83. Lamb, B.T., Sisodia, S.S., Lawler, A.M., Slunt, H.H., Kitt, C.A., Kearns, W.G., Pearson, P.L., Price, D.L. & Gearhart, J.D. (1993) Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat Genet 5, 22-30.
84. Larson, J., Lynch, G., Games, D. & Seubert, P. (1999) Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice. Brain Res 840, 23-35
85. Laurent, B., Thomas-Anterion, C. & Allegri, R.F. (1998) Mémoires et démences. Rev Neurol 154, 2S, 33-49.
86. Lewis, J., Dickson, D.W., Lin, W.L., Chisholm, L., Corral, A., Jones, G., Yen, S.H., Sahara, N., Skipper, L., Yager, D., Eckman, C., Hardy, J., Hutton, M. & McGowan, E. (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science 293, 1487-1491.
87. Lewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Paul Murphy, M. & Baker, M., Yu X., Duff, K., Hardy, J., Corral, A., Lin, W.L., Yen, S.H., Dickson, D.W., Davies, P. & Hutton, M. (2000) Neurofibrillary tangles, amyotrophy and progressive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 25, 402-405.
88. Lim, G.P., Yang, F., Chu, T., Chen, P., Beech, W., Teter, B., Tran, T., Ubeda, O., Ashe, K.H., Frautschy, S.A. & Cole, G.M. (2000) Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J Neurosci 20, 5709-5714.
89. Lim, G.P., Yang, F., Chu, T., Gahtan, E., Ubeda, O., Beech, W., Overmier, J.B., Hsiao-Ashec, K., Frautschy, S.A. & Cole, G.M. (2001) Ibuprofen effects on Alzheimer pathology and open field activity in APPsw transgenic mice. Neurobiol Aging 22, 983-991.
90. Mandelkow, E.M. & Mandelkow, E. (1998) Tau in Alzheimer's disease. Trends Cell Biol 8, 425-427.
91. Masliah, E., Sisk, A., Mallory, M. & Games, D. (2001) Neurofibrillary pathology in transgenic mice overexpressing V717F β-amyloid precursor protein. J Neuropathol Exp Neurol 60, 357-368.
92. Masliah, E., Sisk, A., Mallory, M., Mucke, L., Schenk, D. & Games, D. (1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F β-amyloid precursor protein and Alzheimer's disease. J. Neurosci 16, 5795-4811.
93. Masters, C.L., Simms, G., Weinman, N.A., Multhaup, G., McDonald, B.L. & Beyreuther, K. (1985) Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci USA 82, 4245-4249.
94. Moechars, D., Dewachter, I., Lorent, K., Reverse, D., Baekelandt, V., Naidu, A., Tesseur, I., Spittaels, K., Haute, C.V., Checler, F., Godaux, E., Cordell, B. & Van Leuven, F. (1999) Early phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain J. Biol Chem 274, 6483-6492.
95. Moran, P.M., Higgins, L.S., Cordell, B. & Moser, P.C. (1995) Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human β-amyloid precursor protein. Proc Natl Acad Sci USA 92, 5341-5345.
96. Morgan, D., Diamond, D.M., Gottschall, P.E., Ugen, K.E., Dickey, C., Hardy, J., Duff, K., Jantzen, P., DiCarlo, G., Wilcock, D., Connor, K., Hatcher, J., Hope, C., Gordon, M. & Arendash, G.W. (2000) Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982-985.
97. Mucke, L., Masliah, E., Johnson, W.B., Ruppe, M.D., Alford, M., Rockenstein, E.M., Forss-Petter, S., Pietropaolo, M., Mallory, M. & Abraham C.R. (1994) Synaptotrophic effects of human amyloid β protein precursors in the cortex of transgenic mice. Brain Res 666, 151-671.
98. Oyama, F., Sawamura, N., Kobayashi, K., Morishima-Kawashima, M., Kuramochi, T., Ito, M., Tomita, T., Maruyama, K., Saido, T.C., Iwatsubo, T., Capell, A., Walter, J., Grunberg, J., Ueyama, Y., Haass, C. & Ihara, Y. (1998) Mutant presenilin 2 transgenic mouse: effect on an age-dependent increase of amyloid β-protein 42 in the brain. J Neurochem 71, 313-322.
99. Pearson, B.E. & Choi, T.K. (1993) Expression of the human β-amyloid precursor protein gene from a yeast artificial chromosome in transgenic mice. Proc Natl Acad Sci USA 90, 10578-10582.
100. Perry, R.J. & Hodges, J.R. (1999) Attention and executive deficits in Alzheimer's disease. A critical review. Brain 122, 383-404.
101. Phinney, A.L., Deller, T., Stalder, M., Calhoun, M.E., Frotscher, M., Sommer, B., Staufenbiel, M. & Jucker, M. (1999) Cerebral amyloid induces aberrant axonal sprouting and ectopic terminal formation in amyloid precursor protein transgenic mice. J Neurosci 19, 8552-8559.
102. Pompl, P.N., Mullan, M.J., Bjugstad, K. & Arendash, G.W. (1999) Adaptation of the circular platform spatial memory task for mice: use in detecting cognitive impairment in the APPsw transgenic mouse model for Alzheimer's disease. J Neurosci Meth 87, 87-95.
103. Price, D.L. & Sisodia, S.S. (1998) Mutant genes in familial Alzheimer's disease and transgenic models. Annu Rev Neurosci 21, 479-505.
104. Quon, D., Wang, Y., Catalano, R., Scardina, J.M., Murakami, K. & Cordell, B. (1991) Formation of β-amyloid protein deposits in brains of transgenic mice. Nature 352, 239-241.
105. Refolo, L.M., Pappolla, M.A., LaFrancois, J., Malester, B., Schmidt, S.D., Thomas-Bryant, T., Tint, G.S., Wang, R., Mercken, M., Petanceska, S.S. & Duff, K.E. (2001) A cholesterol-lowering drug reduces β-amyloid pathology in a transgenic mouse model of Alzheimer's disease. Neurobiol Dis 8, 890-899.
106. Reibaud, M., Obinu, M.C., Ledent, C., Parmentier, M., Bohme, G.A. & Imperato, A (1999) Enhancement of memory in cannabinoid CB1 receptor knock-out mice. Eur J Pharmacol 379, R1-R2.
107. Rockenstein, E.M., McConlogue, L., Tan, H., Power, M., Masliah, E. & Mucke, L. (1995) Levels and alternative splicing of amyloid β protein precursor (APP) transcripts in brains of APP transgenic mice and humans with Alzheimer's disease. J Biol Chem 270, 28257-28267.
108. Saitoh, T., Sundsmo, M., Roch, J.M., Kimura, N., Cole, G., Schubert, D., Oltersdorf, T. & Schenk, D.B. (1989) Secreted form of amyloid β protein precursor is involved in the growth regulation of fibroblasts. Cell 58, 625-622.
109. Sandhu, F.A., Salim, M. & Zain, S.B. (1991) Expression of the human βamyloid protein of Alzheimer's disease specifically in the brains of transgenic mice. J Biol Chem 266, 21331-21334
110. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K, Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D. & Seubert, P. (1999) Immunization with amyloid-β attenuates Alzheimerdisease-like pathology in the PDAPP mouse. Nature 400, 173-177
111. Selkoe, D.J. (1994) Cell biology of the amyloid β-protein precursor and the mechanism of Alzheimer's disease. Annu Rev Cell Biol 10, 373-403.
112. Selkoe, D.J. (1998) The cell biology of β-amyloid precursor protein and presenilin in Alzheimer's disease Trends Cell Biol 8, 447-453
113. Sigurdsson, E.M., Scholtzova, H., Mehta, P.D., Frangione, B. & Wisniewski, T. (2001) Immunization with a nontoxic/nonfibrillar amyloid-β homologous peptide reduces Alzheimer's disease-associated pathology in transgenic mice. Am J Pathol 159, 439-447.
114. Small, D.H., Nurcombe, V., Reed, G., Clarris, H., Moir, R., Beyreuther, K. & Masters, C.L. (1994) A heparin-binding domain in the amyloid protein precursor of Alzheimer's disease is involved in the regulation of neurite outgrowth. J Neurosci 14, 2117-2127.
115. Stalder, M., Phinney, A., Probst, A., Sommer, B., Staufenbiel, M. & Jucker, M. (1999) Association of microglia with amyloid plaques in brains of APP23 transgenic mice. Am J Pathol 154, 1673-1684.
116. Strittmatter, W.J. & Roses, A.D. (1996) Apolipoprotein E and Alzheimer's disease. Ann Rev Neurosci 19, 53-77.
117. Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.H., Mistl, C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Paganetti, P.A., Waridel, C., Calhoun, M.E., Jucker, M., Probst, A., Staufenbiel, M. & Sommer, B. (1997) Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc Natl Acad Sci USA 94, 13287-13292.
118. Tang, Y.P., Shimizu, E., Dube, G.R., Rampon, C., Kerchner, G.A., Zhuo, M., Liu, G. & Tsien, J.Z. (1999) Genetic enhancement of learning and memory in mice. Nature 401, 63-69
119. Terai, K., Iwai, A., Kawabata, S., Tasaki, Y., Watanabe, T., Miyata, K. & Yamaguchi, T. (2001) β-amyloid deposits in transgenic mice expressing human β-amyloid precursor protein have the same characteristics as those in Alzheimer's disease. Neuroscience 104, 299-310.
120. Tomidokoro, Y., Ishiguro, K., Harigaya, Y., Matsubara, E., Ikeda, M., Park, J.M., Yasutake, K., Kawarabayashi, T., Okamoto, K. & Shoji, M. (2001) Aβ amyloidosis induces the initial stage of tau accumulation in APPsw mice Neurosci Lett 299, 169-172.
121. Westerman, M.A., Cooper-Blacketer, D., Mariash, A., Kotilinek, L., Kawarabayashi, T., Younkin, L.H., Carlson, G.A., Younkin, S.G. & Ashe, K.H. (2002) The relationship between Aβ and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci 22, 1858-1867.
122. Whiston, J.S., Selkoe, D.J. & Cotman, C.W. (1989) Amyloid β protein enhances the survival of hippocampal neurons in vitro. Science 243, 1488-1490.
123. Wirak, D.O., Bayney, R., Ramabhadran, TV., Fracasso, R.P., Hart, J.T., Hauer, P.E., Hsiau, P., Pekar, S.K., Scangos, G.A., Trapp, B.D. & Unterbeck, A.J. (1991) Deposits of amyloid β protein in the central nervous system of transgenic mice. Science 253, 323-325.
124. Wong, TP., Debeir, T., Duff, K. & Cuello, A.C. (1999) Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes J Neurosci 19, 2706-2716.
125. Yamaguchi, F., Richards, S.J., Beyreuther, K., Salbaum, M., Carlson, G.A. & Dunnett, S.B. (1991) Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory. Neurorepot 2, 781-784.