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Journal of Neural Transmission

, Volume 119, Issue 2, pp 173–195 | Cite as

Recent rodent models for Alzheimer’s disease: clinical implications and basic research

  • Nady Braidy
  • Pablo Muñoz
  • Adrian G. Palacios
  • Gloria Castellano-Gonzalez
  • Nibaldo C. Inestrosa
  • Roger S. Chung
  • Perminder Sachdev
  • Gilles J. Guillemin
Dementias - Review article

Abstract

Alzheimer’s disease (AD) is the most common origin of dementia in the elderly. Although the cause of AD remains unknown, several factors have been identified that appear to play a critical role in the development of this debilitating disorder. In particular, amyloid precursor protein (APP), tau hyperphosphorylation, and the secretase enzymes, have become the focal point of recent research. Over the last two decades, several transgenic and non-transgenic animal models have been developed to elucidate the mechanistic aspects of AD and to validate potential therapeutic targets. Transgenic rodent models over-expressing human β-amyloid precursor protein (β-APP) and mutant forms of tau have become precious tools to study and understand the pathogenesis of AD at the molecular, cellular and behavioural levels, and to test new therapeutic agents. Nevertheless, none of the transgenic models of AD recapitulate fully all of the pathological features of the disease. Octodon degu, a South American rodent has been recently found to spontaneously develop neuropathological signs of AD in old age. This review aims to address the limitations and clinical relevance of transgenic rodent models in AD, and to highlight the potential for O. degu as a natural model for the study of AD neuropathology.

Keywords

Alzheimer’s disease Animal models Octodon degu Amyloid-β Tau phosphorylation Transgenic models 

Notes

Acknowledgments

We thank the Alzheimer’s Association (USA), the University of New South Wales, the Rebecca L. Cooper Medical Foundation, the Perpetual Foundation, the Baxter Foundation, the Mason Foundation, the Curran Foundation, the National Health and Medical Research Council (NHMRC) and Alzheimer Australia for supporting our work. A.G.P.’s and P.M.’s research was partially support by a FIRCA NIH grant to Alfredo Kirkwood 1 R03 TW007171-01 A1 and Iniciativa Cientifica Milenio CINV IC09-022-P.

References

  1. Abraham C, Selkoe D, Potter H, Price D, Cork L (1989) α1-Antichymotrypsin is present together with the β-protein in monkey brain amyloid deposits. Neuroscience 32:196–198CrossRefGoogle Scholar
  2. Alonso Adel C, Mederlyova A, Novak M, Grundke-Iqbal I, Iqbal K (2004) Promotion of hyperphosphorylation by frontotemporal dementia tau mutations. J Biol Chem 279:34873–34881PubMedCrossRefGoogle Scholar
  3. Alonso Adel C, Li B, Grundke-Iqbal I, Iqbal K (2006) Polymerization of hyperphosphorylated tau into filaments eliminates its inhibitory activity. Proc Natl Acad Sci USA 103:8864–8869PubMedCrossRefGoogle Scholar
  4. Alonso AC, Grundke-Iqbal I, Iqbal K (1996) Alzheimer’s disease hyperphosphorylated tau sequesters normal tau into tangles of filaments and disassembles microtubules. Nat Med 2:783–787PubMedCrossRefGoogle Scholar
  5. Alonso AD, Zaidi T, Novak M, Barra HS, Grundke-Iqbal I, Iqbal K (2001) Interaction of tau isoforms with Alzheimer’s disease abnormally hyperphosphorylated tau and in vitro phosphorylation into the disease-like protein. J Biol Chem 276:37967–37973PubMedCrossRefGoogle Scholar
  6. Ardiles A, Barrientos S, Araya J, Tapia Rojas C, Inestrosa N, Kirkwood A, Palacios A (2011) β-Amyloid dodecamers and hyperphosphorylated Tau correlates with synaptic and cognitive impairments in aged Octodon degus. Paper presented at the Reunión Anual Sociedad Chilena de Neurociencia, Las Cruces, ChileGoogle Scholar
  7. Arends YM, Duyckaerts C, Rozemuller JM, Eikelenboom P, Hauw JJ (2000) Microglia, amyloid and dementia in alzheimer disease: a correlative study. Neurobiol Aging 21:39–47PubMedCrossRefGoogle Scholar
  8. Arendt T, Stieler J, Strijkstra A, Hut R, Rudiger J (2003) Reversible paired helical filament-like phosphorylation of tau is an adaptive process associated with neuronal plasticity in hibernating animals. J Neurosci 23:6972–6981PubMedGoogle Scholar
  9. Asberom T, Zhao Z, Bara TA, Clader JW, Greenlee WJ, Hyde LA, Josien HB, Li W, McPhail AT, Nomeir AA, Parker EM, Rajagopalan M, Song L, Wong GT, Zhang L, Zhang Q, Pissarnitski DA (2007) Discovery of gamma-secretase inhibitors efficacious in a transgenic animal model of Alzheimer’s disease. Bioorg Med Chem Lett 17:511–516PubMedCrossRefGoogle Scholar
  10. Asuni AA, Boutajangout A, Quartermain D, Sigurdsson EM (2007) Immunotherapy targeting pathological tau conformers in a tangle mouse model reduces brain pathology with associated functional improvements. J Neurosci 27:9115–9129PubMedCrossRefGoogle Scholar
  11. Atamna H, Frey WH II, Ko N (2009) Human and rodent amyloid-β peptides differentially bind heme: Relevance to the human susceptibility to Alzheimer’s disease. Arch Biochem Biophys 487:59–65PubMedCrossRefGoogle Scholar
  12. Bate C, Boshuizen RS, Langeveld JP, Williams A (2002) Temporal and spatial relationship between the death of PrP-damaged neurones and microglial activation. Neuroreport 13:1695–1700PubMedCrossRefGoogle Scholar
  13. Benatar M, Polak M, Kaplan S, Glass J (2006) Preventing familial amyotrophic lateral sclerosis: is a clinical trial feasible? J Neurol Sci 251:3–9PubMedCrossRefGoogle Scholar
  14. Bons N, Mestre N, Petter A (1991) Senile plaques and neurofibrillary changes in the brain of aged lemurian primate, Microcebus murinus. Neurobiol Aging 13:99–105CrossRefGoogle Scholar
  15. Bons N, Mestre N, Richie K, Petter A, Podlisny M, Selkoe D (1994) Identification of amyloid beta protein in the brain of the small, short-lived lemurian primate Microcebus marinus. Neurobiol Aging 15:215–220PubMedCrossRefGoogle Scholar
  16. Bons N, Rieger F, Prudhomme D, Fisher A, Krause KH (2006) Microcebus murinus: a useful primate model for human cerebral aging and Alzheimer’s disease? Genes Brain Behav 5:120–130PubMedCrossRefGoogle Scholar
  17. Boutajangout A, Quartermain D, Sigurdsson EM (2010) Immunotherapy targeting pathological tau prevents cognitive decline in a new tangle mouse model. J Neurosci 30:16559–16566PubMedCrossRefGoogle Scholar
  18. Brendza RP, Bales KR, Paul SM, Holtzman DM (2002) Role of apoE/Aβ interactions in Alzheimer’s disease: insights from transgenic mouse models. Mol Psychiatry 7:132–135PubMedCrossRefGoogle Scholar
  19. Buee L, Bussiere T, Buee-Scherrer V, Delacourte A, Hof PR (2000) Tau protein isoforms, phosphorylation and role in neurodegenerative disorders. Brain Res Brain Res Rev 33:95–130Google Scholar
  20. Calhoun ME, Wiederhold KH, Abramowski D, Phinney AL, Probst A (1998) Neuron loss in APP transgenic mice. Nature 395:755–756PubMedCrossRefGoogle Scholar
  21. Carrodeguas J, Rodolosse A, Garza M, Sanz-Clemente A, Perez-Pe R, Lacosta A, Dominguez L, Monleon I, Sanchez-Diaz R, Sorribas V, Sarasa M (2005) The chick embryo appears as a natural model for research in beta-amyloid precursor protein processing. Neuroscience 134:1285–1300PubMedCrossRefGoogle Scholar
  22. Chan AW (2004) Transgenic nonhuman primates for neurodegenerative diseases. Reprod Biol Endocrinol 2:39PubMedCrossRefGoogle Scholar
  23. Cherny RA, Atwood CS, Xilinas ME, Gray DN, Jones WD, McLean CA, Barnham KJ, Volitakis I, Fraser FW, Kim Y, Huang X, Goldstein LE, Moir RD, Lim JT, Beyreuther K, Zheng H, Tanzi RE, Masters CL, Bush AI (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice. Neuron 30:665–676PubMedCrossRefGoogle Scholar
  24. Chishti MA, Yang DS, Janus C, Phinney AL, 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 PE, Carlson GA (2001) Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695. J Biol Chem 276:21562–21570PubMedCrossRefGoogle Scholar
  25. Chu W, Qian C (2005) Expressions of Aβ1–40, Aβ1–42, tau202, tau396 and tau404 after intracerebroventricular injection of streptozotocin in rats. Di Yi Jun Yi Da Xue Xue Bao 25:168–170PubMedGoogle Scholar
  26. Dani S (1997) Mechanisms of aging: a survey. In: Dani S, Hori A, Walter G (eds) Principles of neural aging. Elsevier, Amsterdam, pp 5–18Google Scholar
  27. De La Monte SM, Wands J (2005) Review of insulin and insulin-like growth factor expression, signalling, and malfunction in the central nervous system: relevance to Alzheimer’s disease. J Alzheimers Dis 7:45–61Google Scholar
  28. Dedeoglu A, Cormier K, Payton S, Tseitlin KA, Kremsky JN, Lai L, Li X, Moir RD, Tanzi RE, Bush AI, Kowall NW, Rogers JT, Huang X (2004) Preliminary studies of a novel bifunctional metal chelator targeting Alzheimer’s amyloidogenesis. Exp Gerontol 39:1641–1649PubMedCrossRefGoogle Scholar
  29. Delacourte A (1990) General and dramatic glial reaction in Alzheimer brains. Neurology 40:33–37PubMedGoogle Scholar
  30. Delacourte A, Buee L (2005) Animal models of Alzheimer’s disease: a road full of pitfalls. Psychol Neuropsychiatr Vieil 3:261–270PubMedGoogle Scholar
  31. D’Hooge R, De Deyn PP (2001) Applications of the Morris water maze in the study of learning and memory. Brain Res Brain Res Rev 36:60–90PubMedCrossRefGoogle Scholar
  32. Dodart JC, Mathis C, Bales KR, Paul SM (2002) Does my mouse have Alzheimer’s disease? Genes Brain Behav 1:142–155PubMedCrossRefGoogle Scholar
  33. Du P, Wood K, Rosner M, Cunningham D, Tate B, Georghegan K (2007) Dominance of amyloid precursor protein sequence over host cell secretases in determining beta-amyloid profiles studies of interspecies variation and drug action by internally standardised immunoprecipitation/mass spectrometry. J Pharmacol Exp Ther 320:1144–1152PubMedCrossRefGoogle Scholar
  34. Edbauer D, Winkler E, Regula JT, Pesold B, Steiner H, Haass C (2003) Reconstitution of gamma-secretase activity. Nat Cell Biol 5:486–488PubMedCrossRefGoogle Scholar
  35. Feng Z, Cheng Y, Zhang JT (2004) Long-term effects of melatonin or 17 beta-estradiol on improving spatial memory performance in cognitively impaired, ovariectomized adult rats. J Pineal Res 37:198–206PubMedCrossRefGoogle Scholar
  36. Ferri CP, Prince M, Brayne C, Brodaty C, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y (2006) Global prevalence of dementia: a Delphi consensus study. Lancet 366:2112–2117CrossRefGoogle Scholar
  37. Flood D, Howland D, Lin Y-G, Ciallella J, Trusko S, Scott R, Savage M (2003) Aβ deposition in a transgenic rat model of Alzheimer’s disease. Poster 84222. Society for Neuroscience meetingGoogle Scholar
  38. Flood D, Lin YG, Lang DM, Trusko SP, Hirsch JD, Savage MJ, Scott RW, Howland DS (2007) A transgenic rat model of Alzheimer’s disease with extracellular Amyloid-beta deposition. Neurobiol Aging. doi: 10.1016/j.neurobiolaging.2007.10.006
  39. Galimberti D, Scarpini E (2011) Disease-modifying treatments for Alzheimer’s disease. Ther Adv Neurol Disord 4:203–216PubMedCrossRefGoogle Scholar
  40. Gearing M, Rebeck G, Hyman B, Tigges J, Mirra S (1994) Neuropathology and apolipoprotein E profile of aged chimpanzees: implications for Alzheimer’s disease. PNAS 91:9382–9386PubMedCrossRefGoogle Scholar
  41. Gearing M, Tigges J, Mori H, Mirra S (1996a) Aβ40 is a major form of β-amyloid in nonhuman primates. Neurobiol Aging 17:903–906PubMedCrossRefGoogle Scholar
  42. Gearing M, Mori H, Mirra S (1996b) Aβ peptide length and apolipoprotein E genotype in Alzheimer’s disease. Ann Neurol 39:395–399PubMedCrossRefGoogle Scholar
  43. Gearing M, Tigges J, Mori H, Mirra S (1997) β-Amyloid (Aβ) deposition in the brains of aged orangutans. Neurobiol Aging 18:139–146PubMedCrossRefGoogle Scholar
  44. German DC, Eisch AJ (2004) Mouse models of Alzheimer’s disease: insight into treatment. Rev Neurosci 15:353–369PubMedCrossRefGoogle Scholar
  45. Ghribi O, Golovko M, Larsen B, Schrag M, Murphy E (2006) Deposition of iron and beta-amyloid plaques is associated with cortical cellular damage in rabbits fed with long-term cholesterol enriched diets. J Neurochem 99:438–449PubMedCrossRefGoogle Scholar
  46. Glabe C (2001) Intracellular mechanisms of amyloid accumulation and pathogenesis in Alzheimer’s disease. J Mol Neurosci 17:137–145PubMedCrossRefGoogle Scholar
  47. Glabe C (2006) Common mechanisms of amyloid oligomer pathogenesis in degenerative disease. Neurobiol Aging 27:570–575PubMedCrossRefGoogle Scholar
  48. Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterisation of a novel cerebrovascular amyloid protein. Biochem Biophys Res Comm 120:885–890PubMedCrossRefGoogle Scholar
  49. Golde TE, Younkin SG (2001) Presenilins as therapeutic targets for the treatment of Alzheimer’s disease. Trends Mol Med 7:264–269PubMedCrossRefGoogle Scholar
  50. Goldman-Rakic P, Brown R (1981) Regional changes of monoamines in cerebral cortex and subcortical structures of aging rhesus monkeys. Neuroscience 6:177–187PubMedCrossRefGoogle Scholar
  51. Gonzalo-Ruiz A, Gonzalez I, Sanz-Anquela J (2003) Effects of beta-amyloid protein on serotoninergic, noradrenergic, and cholinergic markers in neurons of the pontomesencephalic tegmentum in the rat. J Chem Neuroanat 26:153–169PubMedCrossRefGoogle Scholar
  52. Gotz J, Ittner LM (2008) Animal models of Alzheimer’s disease and frontotemporal dementia. Nat Rev Neurosci 9:532–544PubMedCrossRefGoogle Scholar
  53. Gotz J, Nitsch RM (2001) Compartmentalized tau hyperphosphorylation and increased levels of kinases in transgenic mice. Neuroreport 12:2007–2016PubMedCrossRefGoogle Scholar
  54. Gotz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Aβ 42 fibrils. Science 293:1491–1495PubMedCrossRefGoogle Scholar
  55. Gotz J, Streffer JR, David D, Schild A, Hoerndli F, Pennanen L, Kurosinski P, Chen F (2004) Transgenic animal models of Alzheimer’s disease and related disorders: histopathology, behavior and therapy. Mol Psychiatry 9:664–683PubMedGoogle Scholar
  56. Gotz J, Ittner LM, Kins S (2006) Do axonal defects in tau and amyloid precursor protein transgenic animals model axonopathy in Alzheimer’s disease? J Neurochem 98:993–1006PubMedCrossRefGoogle Scholar
  57. Grieb P, Kryczka T, Fiedorowicz M, Frontczak-Baniewicz M, Walski M (2004) Expansion of the Golgi apparatus in rat cerebral cortex following intracerebroventricular injections of streptozotocin. Acta Neurobiol Exp (Wars) 64:481–489Google Scholar
  58. Grunblatt E, Salkovic-Petrisic M, Osmanovic J, Riederer P, Hoyer S (2006) Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein. J NeurochemGoogle Scholar
  59. Gunawardena S, Goldstein LS (2001) Disruption of axonal transport and neuronal viability by amyloid precursor protein mutations in Drosophila. Neuron 32:389–401PubMedCrossRefGoogle Scholar
  60. Halagappa VK, Guo Z, Pearson M, Matsuoka Y, Cutler RG, Laferla FM, MP M (2007) Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease. Neurobiol Dis 26:212–220PubMedCrossRefGoogle Scholar
  61. Hall GF, Lee VM, Lee G, Yao J (2001) Staging of neurofibrillary degeneration caused by human tau overexpression in a unique cellular model of human tauopathy. Am J Pathol 158:235–246PubMedCrossRefGoogle Scholar
  62. Hamann S, Monarch ES, Goldstein FC (2002) Impaired fear conditioning in Alzheimer’s disease. Neuropsychologia 40:1187–1195PubMedCrossRefGoogle Scholar
  63. Hardy J (2006) Has the amyloid cascade hypothesis of Alzheimer’s disease been proved. Curr Alzheimer Res 3:71–73PubMedCrossRefGoogle Scholar
  64. Hardy JA, Higgins GA (1992) Alzheimer’s disease: the amyloid cascade hypothesis. Science 256:184–185PubMedCrossRefGoogle Scholar
  65. Hardy J, Selkoe D (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356PubMedCrossRefGoogle Scholar
  66. Hare B, Brown M, Williamson C, Tomasello M (2002) The domestication of social cognition in dogs. Science 298:1634–1636PubMedCrossRefGoogle Scholar
  67. Harper J, Wong S, Lieber C, Lansbury P (1997) Observation of metastable Aβ-amyloid protofibrils by atomic force microscopy. Chem Biol 4:119–125PubMedCrossRefGoogle Scholar
  68. Hartig W, Bruckner G, Schmidt C, Brauer K, Bodewitz G, Turner J, Bigl V (1997) Co-localisation of β-amyloid peptides, apolipoprotein E and glial markers in senile plaques in the prefrontal cortex of old rhesus monkeys. Brain Res 751:315–322PubMedCrossRefGoogle Scholar
  69. Hartig W, Klein C, Brauer K, Schuppel K, Arendt T, Bruckner G, Bigl V (2000) Abnormally phosphorylated protein tau in the cortex of aged individuals of various mammalian orders. Acta Neuropathol 100:305–312PubMedCrossRefGoogle Scholar
  70. Hartig W, Goldhammer S, Bauer U, Wegner F, Wirths O, Bayer T, Grosche J (2010) Concomitant detection of β-amyloid peptides with N-terminal truncation and different C-terminal endings in cortical plaques from cases with Alzheimer’s disease, senile monkeys and triple transgenic mice. J Chem Neuroanat 40:82–92PubMedCrossRefGoogle Scholar
  71. Hashimoto M, Rockenstein E, Crews L, Masliah E (2003) Role of protein aggregation in mitochondrial dysfunction and neurodegeneration in Alzheimer’s and Parkinson’s diseases. Neuromol Med 4:21–36CrossRefGoogle Scholar
  72. Higgins GA, Jacobsen H (2003) Transgenic mouse models of Alzheimer’s disease: phenotype and application. Behav Pharmacol 14:419–438PubMedGoogle Scholar
  73. Holtzman DM, Bales KR, Wu S, Bhat P, Parsadanian M, Sartorious LJ (1999) Expression of human apolipoprotein E reduces amyloid beta deposition in a mouse model of Alzheimer’s disease. J Clin Invest 103:R15–R21PubMedCrossRefGoogle Scholar
  74. Holtzman DM, Bales KR, Tenkova T, Fagan AM, Parsadanian M, LJ S (2000) Apolipoprotein E isoform-dependent amyloid deposition and neuritic degeneration in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 97:2892–2897PubMedCrossRefGoogle Scholar
  75. Howlett DR, Richardson JC (2009) The pathology of APP transgenic mice: a model of Alzheimer’s disease or simply overexpression of APP? Histol Histopathol 24:83–100PubMedGoogle Scholar
  76. Hoyer S (2000) Brain glucose and energy metabolism abnormalities in sporadic Alzheimer’s disease. Causes and consequences: an update. Exp Gerontol 35:1363–1372PubMedCrossRefGoogle Scholar
  77. Hoyer S (2004) Glucose metabolism and insulin receptor signal transduction in Alzheimer’s disease. Euro J Pharmacol 490:115–125CrossRefGoogle Scholar
  78. Hsiao 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 274:99–102PubMedCrossRefGoogle Scholar
  79. Hussain I, Hawkins J, Harrison D, Hille C, Wayne G, Cutler L, Buck T, Walter D, Demont E, Howes C, Naylor A, Jeffrey P, Gonzalez MI, Dingwall C, Michel A, Redshaw S, Davis JB (2007) Oral administration of a potent and selective non-peptidic BACE-1 inhibitor decreases beta-cleavage of amyloid precursor protein and amyloid-beta production in vivo. J Neurochem 100:802–809PubMedCrossRefGoogle Scholar
  80. Hydea LA, Kazdobaa TM, Grillia M, Lozzaa G, Brussaa R, Zhanga Q, Wonga GT, McCoola MF, Zhanga L, Parkera EM, Higginsa GA (2005) Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice. Behav Brain Res 160:344–355CrossRefGoogle Scholar
  81. Inestrosa NC, Reyes AE, Chacon MA, Cerpa W, Villalon A, Montiel J, Merabachvili G, Aldunate R, Bozinovic F, Aboitiz F (2005) Human-like rodent amyloid-beta-peptide determines Alzheimer pathology in aged wild-type Octodon degu. Neurobiol Aging 26:1023–1028PubMedCrossRefGoogle Scholar
  82. Jawhar S, Wirths O, Schilling S, Graubner S, Demuth H-U, Bayer T (2011) Overexpression of glutaminyl cyclase, the enzyme responsible for pyroglutamate Aβ formation, induces behavioural deficits, and glutaminyl cyclase knock-out rescues the behavioural phenotype in 5×FAD mice. J Bio Chem 286:4454–4460CrossRefGoogle Scholar
  83. Johnson S, Lampert-Etchells M, Pasinetti G, Rozovsky I, Finch C (1992) Complement mRNA in the mammalian brain: responses to Alzheimer’s disease and experimental brain lesioning. Neurobiol Aging 13:641–648PubMedCrossRefGoogle Scholar
  84. Johnstone E, Chaney M, Norris F, Pascual R, Little S (1991) Conservation of the sequence of the Alzheimer’s disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis. Brain Res Mol Brain Res 10:299–305PubMedCrossRefGoogle Scholar
  85. Jolas T, Zhang XS, Zhang Q, Wong G, Del Vecchio R, Gold L, Priestley T (2002) Long-term potentiation is increased in the CA1 area of the hippocampus of APPswe/indCRND8mice. Neurobiol Dis 11:394–409PubMedCrossRefGoogle Scholar
  86. Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, Sisodia S, Malinow R (2003) APP processing and synaptic function. Neuron 37:925–937PubMedCrossRefGoogle Scholar
  87. Kanemaru K, Iwatsubo T, Ihara Y (1996) Comparable amyloid β-protein (Aβ) 42(43) and Aβ40 deposition in aged monkey brain. Neurosci Lett 214:196–198PubMedCrossRefGoogle Scholar
  88. Kelly PH, Bondolfi L, Hunziker D, Schlecht H, Carver K, Maguire E, Abramowski D, Wiederhold K, Sturchler-Pierrat C, Jucker M, Bergmanna R, Staufenbiel M, Sommera B (2003) Progressive age-related impairment of cognitive behavior in APP23 transgenic mice. Neurobiol Aging 24:365–378PubMedCrossRefGoogle Scholar
  89. Kiatipattanasakul W, Nakayama H, Yongsiri S, Chotiapisitkul S, Nakamura S, Kojima H, Doi K (2000) Abnormal neuronal and glial argyrophilic fibrillary structures in the brain of aged individuals of various mammalian orders. Acta Neuropathol 100:305–312CrossRefGoogle Scholar
  90. Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH (2007) SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer’s disease and amyotrophic lateral sclerosis. EMBO J 26:3169–3179PubMedCrossRefGoogle Scholar
  91. Kraemer BC, Zhang B, Leverenz JB, Thomas JH, Trojanowski J, Schellenberg GD (2003) From the cover: neurodegeneration and defective neurotransmission in a Caenorhabditis elegans model of tauopathy. PNAS 100:9980–9985PubMedCrossRefGoogle Scholar
  92. Kulic L, Kurosinski P, Chen F, Tracy J, Mohajeri MH, Li H, Nitsch RM, Gotz J (2006) Active immunization trial in Aβ42-injected P301L tau transgenic mice. Neurobiol Dis 22:50–56PubMedCrossRefGoogle Scholar
  93. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155–184PubMedCrossRefGoogle Scholar
  94. Lewis J, McGowan E, Rockwood J, Melrose H, Nacharaju P, Van Slegtenhorst M (2000) Neurofibrillary tangles, amyotrophy and passive motor disturbance in mice expressing mutant (P301L) tau protein. Nat Genet 25:402–405PubMedCrossRefGoogle Scholar
  95. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G (2001) Enhanced neurofibrillary degeneration in transgenic mice expressing mutant Tau and APP. Science 293:1487–1491PubMedCrossRefGoogle Scholar
  96. Li T (2004) Recent progress in Alzheimer’s disease: animal models lead the way. Drug Discov Today Dis Models 1:145–149CrossRefGoogle Scholar
  97. Li L, Cao D, Kim H, Lester R, Fukuchi K (2006) Simvastatin enhances learning and memory independent of amyloid load in mice. Ann Neurol 60:729–739PubMedCrossRefGoogle Scholar
  98. Liberski P, Sikorska B, Bratosiewicz-Wasik J, Gajdusek D, Brown P (2004) Neuronal cell death in transmissible spongiform encephalopathies (prion diseases) revisited: from apoptosis to autophagy. Int J Biochem Cell Biol 36:2473–2490PubMedCrossRefGoogle Scholar
  99. Lim GP, Calon F, Morihara T, Yang F, Teter B, Ubeda O, Salem N Jr, Frautschy SA, GM C (2005) A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model. J Neurosci 25:3032–3040PubMedCrossRefGoogle Scholar
  100. Lopez EM, Bell KFS, Ribeiro-da-Silva A, Cuello AC (2004) Early changes in the neurons of the hippocampus and neocortex in transgenic rats expressing intracellular human Aβ. J Alzheimers Dis 6:421–431PubMedGoogle Scholar
  101. Maccioni RB, Munoz JP, Barbeito L (2001) The molecular bases of Alzheimer’s disease and other neurodegenerative disorders. Arch Med Res 32:367–381PubMedCrossRefGoogle Scholar
  102. Martin L, Sisodia S, Koo E, Cork L, Dellovade T, Weidemann A, Beyreuther K, Masters C, Price D (1991) Amyloid precursor protein in aged nonhuman primates. Proc Natl Acad Sci USA 88:1461–1465PubMedCrossRefGoogle Scholar
  103. Masters CL, Simms G, Weinman NA, Maulthaup G, McDonald BL, Beyreuther K (1985) Amyloid plaque core protein in Alzheimer’s disease and Downs syndrome. Proc Natl Acad Sci USA 82:4245–4249PubMedCrossRefGoogle Scholar
  104. Mattson MP (2004) Pathway towards and away from Azheimer’s disease. Nature 430:630–639CrossRefGoogle Scholar
  105. Mesulam MM, Geula C (1988) Acetylcholinesterase-rich pyramidal neurons in the human neocortex and hippocampus: absence at birth, development during the life span, and dissolution in Alzheimer’s disease. Ann Neurol 24:765–773PubMedCrossRefGoogle Scholar
  106. Mina E, Demuro A, Kayed R, Milton S, Parker I, Glabe C (2004) Membrane disruption and elevated intracellular calcium as a common mechanism of amyloid oligomer-induced neurodegeneration. Neurosci Abstr. 449:20Google Scholar
  107. Minamide L, Striegel A, Boyle J, Meberg P, Bamburg J (2000) Neurodegenerative stimuli induce persistent ADF/cofilin-actin rods that disrupt distal neurite function. Nat Cell Biol 2:628–636PubMedCrossRefGoogle Scholar
  108. Morgan B (1990) Complement. Clinical aspects and relevance to disease. Academic Press, San DiegoGoogle Scholar
  109. Nakumura S, Tamaoka A, Sawamura N, Shoji S, Nakayama H, Ono F, Sakakibara I, Yoshikawa Y, Mori H, Goto N, Doi K (1995) Carboxyl end-specific monoclonal antibodies to amyloid β protein (Aβ) subtypes (Aβ40 and Aβ42(43)) differentiate Aβ in senile plaques and amyloid angiopathy in brains of aged cynomolgus monkeys. Neurosci Lett 201:151–154CrossRefGoogle Scholar
  110. Nicholl JA, Wilkinson D, Holmes C, Steart P, Markham H, Weller RO (2003) Neuropathology of human Alzheimer’s disease after immunisation with amyloid-beta peptide: a case report. Nat Med 9:448–452CrossRefGoogle Scholar
  111. Nichols D, Day J, Laping N, Johnson S, Finch C (1993) GFAP mRNA increases with age in rat and human tissue. Neurobiol Aging 14:421–429PubMedCrossRefGoogle Scholar
  112. Nikolic WV, Bai Y, Obregon D, Hou H, Mori T, Zeng J, Ehrhart J, Shytle RD, Giunta B, Morgan D, Town T, Tan J (2007) Transcutaneous beta-amyloid immunization reduces cerebral beta-amyloid deposits without T cell infiltration and microhemorrhage. Proc Natl Acad Sci USA 104:2507–2512PubMedCrossRefGoogle Scholar
  113. Oakley H, Cole S, Logan S, Maus E, Shao P, Craft J, Guillozet-Bongaarts A, Ohno M, Disterhoft J, Eldik L, Berry R, Vassar R (2006) Intraneuronal β-amyloid aggregates, neurodegeneration, and neuronal loss in transgenic mice with five familial Alzheimer’s disease mutations: potential factors in amyloid plaque formation. J Neurosci 26:10129–10140PubMedCrossRefGoogle Scholar
  114. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, Metherate R, Mattson MP, Akbari Y, LaFerla FM (2003) Triple-transgenic model of Alzheimer’s disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39:409–421PubMedCrossRefGoogle Scholar
  115. Pathan A, Viswanad B, Sonkusare S, Ramarao P (2006) Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sci 79:2209–2216PubMedCrossRefGoogle Scholar
  116. Pennanen L, Welzl H, D’Adamo P, Nitsch RM, Gotz J (2004) Accelerated extinction of conditioned taste aversion in P301L tau transgenic mice. Neurobiol Dis 15:500–509PubMedCrossRefGoogle Scholar
  117. Permanne B, Adessi C, Saborio GP, Fraga S, Frossard MJ, Van Dorpe J (2002) Reduction of amyloid load and cerebral damage in a transgenic mouse model of Alzheimer’s disease by treatment with a beta-sheet breaker peptide. FASEB J 16:860–862PubMedGoogle Scholar
  118. Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M (2002) Cerebral hemorrhage after passive anti-Aβ immunotherapy. Science 298:1379PubMedCrossRefGoogle Scholar
  119. Podlisny M, Tolan D, Selkoe D (1991) Homology of the amyloid beta protein precursor in monkey and human supports a primate model for beta amyloidosis in Alzheimer’s disease. Am J Pathol 138:1423–1435PubMedGoogle Scholar
  120. Poduri A, Gearing M, Rebeck G, Mirra S, Tigges J, Hyman B (1994) Apolipoprotein E4 and beta amyloid in senile plaques and cerebral blood vessels of aged rhesus monkeys. Am J Pathol 144:1183–1187PubMedGoogle Scholar
  121. Poirier R, Wolfer DP, Welzl H, Tracy J, Galsworthy MJ, Nitsch RM, Mohajeri MH (2006) Neuronal neprilysin overexpression is associated with attenuation of Aβ-related spatial memory deficit. Neurobiol Dis 24:475–483PubMedCrossRefGoogle Scholar
  122. Ponce A, Cerpa W, Muñoz P, Inestrosa N, Palacios A (2007) Aging and spatial memory in the rodent Octodon degus. In: IIIrd Neurotoxicity Society meeting, Pucon, Chile, April 2007Google Scholar
  123. Popovic N, Bano-Otalora B, Rol MA, Caballero-Bleda M, Madid JA, Popovic M (2009) Aging and time-of-day effects on anxiety in female Octodon degus. Behav Brain Res 200:117–121PubMedCrossRefGoogle Scholar
  124. Prasad CV, Zheng M, Vig S, Bergstrom C, Smith DW, Gao Q, Yeola S, Polson CT, Corsa JA, Guss VL, Loo A, Wang J, Sleczka BG, Dangler C, Robertson BJ, Hendrick JP, Roberts SB, Barten DM (2007) Discovery of (S)-2-((S)-2-(3,5-difluorophenyl)-2-hydroxyacetamido)-N-((S,Z)-3-methyl-4-oxo-4,5-dihydro-3H-benzo[d][1,2]diazepin-5-yl)propanamide (BMS-433796): a gamma-secretase inhibitor with Aβ lowering activity in a transgenic mouse model of Alzheimer’s disease. Bioorg Med Chem LettGoogle Scholar
  125. Prickaerts J, Fahrig T, Blokland A (1999) Cognitive performance and biochemical markers in septum, hippocampus and striatum of rats after an i.c.v. injection of streptozocin: a correlation analysis. Behav Brain Res 102:73–88PubMedCrossRefGoogle Scholar
  126. Puglielli L, Konopka G, Pack-Chung E, Ingano LA, Berezovska O, Hyman BT, Chang TY, Tanzi RE, Kovacs DM (2001) Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid beta-peptide. Nat Cell Biol 3:905–912PubMedCrossRefGoogle Scholar
  127. Puglielli L, Tanzi RE, Kovacs DM (2003) Alzheimer’s disease: the cholesterol connection. Nat Neurosci 6:345–351PubMedCrossRefGoogle Scholar
  128. Pugliese MJM, Mahy N, Ferrer I (2006) Diffuse beta-amyloid plaques and hyperphosphorylated tau are unrelated processes in aged dogs with behavioural deficits. Acta Neuropathol (Berl) 112:175–183CrossRefGoogle Scholar
  129. Rahman A, Ting K, Cullen KM, Brew BJ, Braidy N, Guillemin GJ (2009) The excitotoxin quinolinic acid induces tau phosphorylation in human neurons. PLoS ONE 4:e6344PubMedCrossRefGoogle Scholar
  130. Rapp P, Amaral D (1992) Individual differences in the cognitive and neurobiological consequences of normal aging. Trends Neurosci 15:340–345PubMedCrossRefGoogle Scholar
  131. Rezai-Zadeh K, Shytle D, Sun N, Mori T, Hou H, Jeanniton D, Ehrhart J, Townsend K, Zeng J, Morgan D, Hardy J, Town T, Tan J (2005) Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J Neurosci 25:8807–8814PubMedCrossRefGoogle Scholar
  132. Richards JG, Higgins GA, Ouagazzal AM, Ozmen L, Kew JNC, Bohrmann B, Malherbe P, Brockhaus M, Loetscher H, Czech C, Huber G (2003) PS2APP transgenic mice, coexpressing hPS2mut and hAPPswe, show age-related cognitive deficits associated with discrete brain amyloid deposition and inflammation. J Neurosci 23:8989–9003PubMedGoogle Scholar
  133. Ritchie CW, Bush AI, Mackinnon A, Macfarlane S, Mastwyk M, MacGregor L, Kiers L, Cherny R, Li QX, Tammer A, Carrington D, Mavros C, Volitakis I, Xilinas M, Ames D, Davis S, Beyreuther K, Tanzi RE, Masters CL (2003) Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Aβ amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch Neurol 60:1685–1691PubMedCrossRefGoogle Scholar
  134. Rocchi A, Pellegrini S, Siciliano G, Mum L (2003) Causative and susceptibility genes for Alzheimer’s disease: a review. Brain Res Bull 61:1–24PubMedCrossRefGoogle Scholar
  135. Rockenstein E, Torrance M, Mante M, Adame A, Paulino A, Rose JB, Crews L, Moessler H, Masliah E (2006) Cerebrolysin decreases amyloid-beta production by regulating amyloid protein precursor maturation in a transgenic model of Alzheimer’s disease. J Neurosci Res 83:1252–1261PubMedCrossRefGoogle Scholar
  136. Rofina J, van Andel I, van Ederen A, Papaioannou N, Yamaguchi H, Guys E (2000) Canine counterpart of senile dementia of the Alzheimer type: amyloid plaques near capillaries but lack of spatial relationship with activated microglia and macrophages. Amyloid: J Protein Folding Disord 10:86–96CrossRefGoogle Scholar
  137. Russell M, White R, Patel E, Markesbery W, Watson C, Geddes J (1992) Familial influence on plaque formation in the beagle brain. Neuroreport 3:1093–1096PubMedCrossRefGoogle Scholar
  138. Saido T, Iwatsubo T, Mann D, Shimada H, Ihara Y, Kawashima S (1995) Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques. Neuron 14:457–466PubMedCrossRefGoogle Scholar
  139. Saido T, Yamao-Harigaya W, Iwatsubo T, Kawashima S (1996) Amino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain. Neurosci Lett 215:173–176PubMedCrossRefGoogle Scholar
  140. Salkovic-Petrisic M, Tribl F, Schmidt M, Hoyer S, Riederer P (2006) Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to insulin signalling pathway. J Neurochem 96:1005–1015PubMedCrossRefGoogle Scholar
  141. Salvin H, McGreevy P, Sachdev P, Valenzuela M (2011a) The canine sand maze: an appetitive spatial memory paradigm sensitive to age-related change in dogs. J Exp Anal Behav 95:109–118PubMedCrossRefGoogle Scholar
  142. Salvin H, McGreevy P, Sachdev P, Valenzuela M (2011b) The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. Vet J 188:331–336PubMedCrossRefGoogle Scholar
  143. Sarasa M, Gallego M (2006) Alzheimer-like neurodegeneration as a probable cause of cetacean stranding. In: 5th forum of European neuroscience, ViennaGoogle Scholar
  144. Sarasa M, Pesini P (2009) Natural non-transgenic animal models for research in Alzheimer’s disease. Curr Alzheimer Res 6:171–178PubMedCrossRefGoogle Scholar
  145. Satou T, Cummings B, Head E, Nielson K, Hahn F, Milgram N (1997) The progression of beta-amyloid deposition in the frontal cortex of aged canines. Brain Res 774:35–43PubMedCrossRefGoogle Scholar
  146. 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-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400:173–177PubMedCrossRefGoogle Scholar
  147. Schenk DB, Seubert P, Grundman M, Black R (2005) A beta immunotherapy: lessons learned for potential treatment of Alzheimer’s disease. Neurodegener Dis 2:255–260PubMedCrossRefGoogle Scholar
  148. Schubert D, Behl C, Lesley R, Brack A, Dargusch R, Sagara Y (1995) Amyloid peptides are toxic via a common oxidative mechanism. Proc Natl Acad Sci USA 92:1989–1993PubMedCrossRefGoogle Scholar
  149. Schultz C, Braak E, Braak H (1998) A nonhuman primate model for tau-positive cytoskeletal pathology affecting neurons astrocytes and oligodendrocytes. Clin Neuropathol 17:251Google Scholar
  150. Schultz C, Dehghani F, Hubbard G, Thal D, Struckhoff G, Braak E, Braak H (2000a) Filamentous tau pathology in nerve cells, astrocytes and oligodendrocytes of aged baboons. J Neuropathol Exp Neurol 59:39–52PubMedGoogle Scholar
  151. Schultz C, Hubbard B, Rub U, Braak E, Braak H (2000b) Age-related progression of tau pathology in brains of baboons. Neurobiol Aging 21:905–911PubMedCrossRefGoogle Scholar
  152. Sharma M, Gupta Y (2002) Chronic treatment with trans resveratrol prevents intracerebroventricular streptozotocin induced cognitive impairment and oxidative stress in rats. Life Sci 71:2489–2498PubMedCrossRefGoogle Scholar
  153. Siddique Z, Peters A (1999) The effect of aging on pars compacta of the substantia nigra in rhesus monkeys. J Neuropathol Exp Neurol 58:903–920CrossRefGoogle Scholar
  154. Sparks D, Schreurs B (2003) Trace amounts of copper in water induce beta-amyloid plaques and learning deficits in a rabbit model of Alzheimer’s disease. PNAS 100:11065–11069PubMedCrossRefGoogle Scholar
  155. Sparks D, Friedland R, Petanceska S, Schreurs B, Shi J, Perry G (2006) Trace copper levels in the drinking water, but not zinc or aluminium influence CNS Alzheimer-like pathology. J Nutr Health Aging 10:247–254PubMedGoogle Scholar
  156. Speakman J (2005) Body size, energy metabolism and lifespan. J Exp Biol 208:1717–1730PubMedCrossRefGoogle Scholar
  157. Spires TL, Hyman BT (2005) Transgenic models of Alzheimer’s disease: learning from animals. NeuroRx 2:423–437PubMedCrossRefGoogle Scholar
  158. Stieler J, Boerema A, Bullmann T, Kohl F, Strijkstra A (2008) Activity state profile of tau kinases in hibernating animals. In: Lovegrove B, McKechnie A (eds) Hypometabolism in animals: hibernation turpor and cryobiology. University of KwaZulu-Natal, Pietermaritzburg, pp 133–142Google Scholar
  159. Stieler J, Bullmann T, Kohl F, Toien O, Bruckner M, Hartig W, Barnes B, Arendt T (2011) The physiological link between metabolic rate depression and tau phosphorylation in mammalian hibernation. PLoS ONE 6:e14530PubMedCrossRefGoogle Scholar
  160. Suh YH, Checler F (2002) Amyloid precursor protein, presenilins, and α-synuclein: molecular pathogenesis and pharmacological applications in Alzheimer’s disease. Pharm Rev 54:469–525PubMedCrossRefGoogle Scholar
  161. Tanemura K, Murayama M, Akagi T, Hashikawa T, Tominaga T, Ichikawa K (2002) Neurodegeneration with tau accumulation in a transgenic mouse expressing V337M human tau. J Neurosci 22:133–141PubMedGoogle Scholar
  162. Tatebayashi Y, Miyasaka T, Chui DH, Akagi T, Mishima K, Iwasaki K (2002) Tau filament formation and associative memory deficit in aged mice expressing mutant (R406W) human tau. PNAS 99:13896–13901PubMedCrossRefGoogle Scholar
  163. Van Dam D, D’Hooge R, Staufenbiel M, van Ginneken C, van Meir F, De Deyn P (2003) Age-dependent cognitive decline in the APP23 model precedes amyloid deposition. Eur J Neurosci 17:388–396PubMedCrossRefGoogle Scholar
  164. van Groen T, Kadish I, Popović N, Popović M, Caballero-Bleda M, Baño-Otálora B, Vivanco P, Rol MA, Madrid JA (2011) Age-related brain pathology in Octodon degu: blood vessel, white matter and Alzheimer-like pathology. Neurobiol Aging 32(9):1651–1661PubMedCrossRefGoogle Scholar
  165. Vardy ER, Catto AJ, Hooper NM (2005) Proteolytic mechanisms in amyloid-beta metabolism: therapeutic implications for Alzheimer’s disease. Trends Mol Med 11:464–472PubMedCrossRefGoogle Scholar
  166. Vassar R, Bennett BD, Babu-Khan S, Kahn S, Mendiaz EA, Denis P, Teplow DB, Ross S, Amarante P, Loeloff R, Luo Y, Fisher S, Fuller J, Edenson S, Lile J, Jarosinski MA, Biere AL, Curran E, Burgess T, Louis JC, Collins F, Treanor J, Rogers G, Citron M (1999) Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science. 286:735–741PubMedCrossRefGoogle Scholar
  167. Voytko M (1998) Nonhuman primates as models for aging and Alzheimer’s disease. Lab Anim Sci 48:611–617PubMedGoogle Scholar
  168. Walker L (1991) Animal models of cerebral amyloidosis. Bull Clin Neurosci 56:86–96Google Scholar
  169. Walker L (1997) Animal models of cerebral beta-amyloid angiopathy. Brain Res Rev 30:70–84CrossRefGoogle Scholar
  170. Walsh D, Klyubin I, Fadeeva J, Cullen W, Anwyl R, Wolfe M, Rowan M, Selkoe D (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416:535–539PubMedCrossRefGoogle Scholar
  171. Weinstock M, Shoham S (2004) Rat models of dementia based on reductions in regional glucose metabolism, cerebral blood flow and cytochrome oxidase activity. J Neural Transm 111:347–366PubMedCrossRefGoogle Scholar
  172. Whiteman I, Gervasio O, Cullen K, Guillemin G, Jeong E, Witting P, Antao S, Minamide L, Bamburg J, Goldsbury C (2009) Activated actin-depolymerising factor/cofilin sequesters phosphorylated microtubule-associated protein during the assembly of Alzheimer-like neuritic cytoskeletal striations. J Neurosci 29:12994–13005PubMedCrossRefGoogle Scholar
  173. Winton M, Lee E, Sun W, Wong M, Leight S, Zhang B, Trojanowski J, Lee VM-Y (2011) Intraneuronal APP, not free Aβ peptides in 3×Tg-AD mice: Implications for tau versus Aβ-mediated Alzheimer neurodegeneration. J Neurosci 31:7691–7699PubMedCrossRefGoogle Scholar
  174. Wisniewski HM, Ghetti B, Terry R (1973) Neuritic (senile) plaques and filamentous changes in aged rhesus monkeys. J Neuropathol Exp Neurol 32:566–584PubMedCrossRefGoogle Scholar
  175. Wong G, Manfra D, Poulet F, Zhang Q, Josien H, Bara T (2004) Chronic treatment with γ-secretase inhibitor LY-411, 575 inhibit β-amyloid peptide production and alters lymphopoiesis and intestinal cell differentiation. J Biol Chem 279:12876–12882PubMedCrossRefGoogle Scholar
  176. Woodruff-Pak D, Agelan A, Del Valle L (2007) A rabbit model Alzheimer’s disease: valid at neuropathological, cognitive, and therapeutic levels. J Alzheimers Dis 11:371–383PubMedGoogle Scholar
  177. Zucker RS, Regehr WG (2002) Short-term synaptic plasticity. Annu Rev Physiol 64:355–405PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Nady Braidy
    • 1
    • 2
  • Pablo Muñoz
    • 3
  • Adrian G. Palacios
    • 3
  • Gloria Castellano-Gonzalez
    • 4
  • Nibaldo C. Inestrosa
    • 5
  • Roger S. Chung
    • 6
  • Perminder Sachdev
    • 2
    • 7
  • Gilles J. Guillemin
    • 1
    • 4
  1. 1.Department of PharmacologyUniversity of New South WalesSydneyAustralia
  2. 2.School of PsychiatryUniversity of New South WalesSydneyAustralia
  3. 3.Centro Interdiciplinario de Neurociencia de Valparaiso (CINV), Facultad de CienciasUniversidad de ValparaisoValparaisoChile
  4. 4.St Vincent’s Centre for Applied Medical ResearchSydneyAustralia
  5. 5.Centre for Aging and Regeneration (CARE), Faculty of Biological SciencesP. Catholic University of ChileSantiagoChile
  6. 6.Menzies Research InstituteUniversity of TasmaniaHobartAustralia
  7. 7.Neuropsychiatric Institute, Prince of Wales HospitalSydneyAustralia

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