title: Recent rodent models for Alzheimer's disease: clinical implications and basic research.
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.
authors.affiliation: Department of Pharmacology, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.forename: Pablo
authors.initials: P
authors.lastname: Muñoz
authors.forename: Adrian G
authors.initials: AG
authors.lastname: Palacios
authors.forename: Gloria
authors.initials: G
authors.lastname: Castellano-Gonzalez
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
authors.forename: Roger S
authors.initials: RS
authors.lastname: Chung
authors.forename: Perminder
authors.initials: P
authors.lastname: Sachdev
authors.forename: Gilles J
authors.initials: GJ
authors.lastname: Guillemin
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D000818:Animals; D030801:Animals, Genetically Modified; D035843:Biomedical Research / Q000379:methods / Q000639:trends*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D046329:Octodon / Q000235:genetics / Q000502:physiology; D013045:Species Specificity
references.citation: Neuroreport. 2002 Sep 16;13(13):1695-700
references.pmid: 12352629
references.citation: J Pharmacol Exp Ther. 2007 Mar;320(3):1144-52
references.pmid: 17202404
references.citation: J Exp Biol. 2005 May;208(Pt 9):1717-30
references.pmid: 15855403
references.citation: J Chem Neuroanat. 2010 Sep;40(1):82-92
references.pmid: 20347032
references.citation: Neurobiol Dis. 2007 Apr;26(1):212-20
references.pmid: 17306982
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 19;100(17):9980-5
references.pmid: 12872001
references.citation: J Biol Chem. 2004 Mar 26;279(13):12876-82
references.pmid: 14709552
references.citation: Trends Mol Med. 2001 Jun;7(6):264-9
references.pmid: 11378516
references.citation: J Alzheimers Dis. 2007 Jun;11(3):371-83
references.pmid: 17851187
references.citation: J Neurosci. 2005 Sep 21;25(38):8807-14
references.pmid: 16177050
references.citation: Proc Natl Acad Sci U S A. 2007 Feb 13;104(7):2507-12
references.pmid: 17264212
references.citation: Neurobiol Aging. 1997 Mar-Apr;18(2):139-46
references.pmid: 9258890
references.citation: Amyloid. 2003 Jun;10(2):86-96
references.pmid: 12964416
references.citation: Neurobiol Aging. 1996 Nov-Dec;17(6):903-8
references.pmid: 9363802
references.citation: Nature. 1999 Jul 8;400(6740):173-7
references.pmid: 10408445
references.citation: J Pineal Res. 2004 Oct;37(3):198-206
references.pmid: 15357665
references.citation: Nat Cell Biol. 2003 May;5(5):486-8
references.pmid: 12679784
references.citation: Brain Res. 1997 Mar 21;751(2):315-22
references.pmid: 9099821
references.citation: Neurobiol Dis. 2006 Apr;22(1):50-6
references.pmid: 16289870
references.citation: Exp Gerontol. 2004 Nov-Dec;39(11-12):1641-9
references.pmid: 15582280
references.citation: J Neurochem. 2006 Aug;98(4):993-1006
references.pmid: 16787410
references.citation: J Neurosci. 2010 Dec 8;30(49):16559-66
references.pmid: 21147995
references.citation: Science. 1999 Oct 22;286(5440):735-41
references.pmid: 10531052
references.citation: J Neurol Sci. 2006 Dec 21;251(1-2):3-9
references.pmid: 17005203
references.citation: Nat Cell Biol. 2000 Sep;2(9):628-36
references.pmid: 10980704
references.citation: Behav Brain Res. 2005 May 28;160(2):344-55
references.pmid: 15863231
references.citation: J Neuropathol Exp Neurol. 1973 Oct;32(4):566-84
references.pmid: 4202280
references.citation: J Clin Invest. 1999 Mar;103(6):R15-R21
references.pmid: 10079115
references.citation: Ther Adv Neurol Disord. 2011 Jul;4(4):203-16
references.pmid: 21765871
references.citation: Pharmacol Rev. 2002 Sep;54(3):469-525
references.pmid: 12223532
references.citation: Bioorg Med Chem Lett. 2007 Jul 15;17(14):4006-11
references.pmid: 17502137
references.citation: Ann Neurol. 1996 Mar;39(3):395-9
references.pmid: 8602762
references.citation: Mol Psychiatry. 2004 Jul;9(7):664-83
references.pmid: 15052274
references.citation: Neuroscience. 1981;6(2):177-87
references.pmid: 6111765
references.citation: Am J Pathol. 2001 Jan;158(1):235-46
references.pmid: 11141497
references.citation: Neuroreport. 1992 Dec;3(12):1093-6
references.pmid: 1493222
references.citation: Neuropsychologia. 2002;40(8):1187-95
references.pmid: 11931922
references.citation: Neurobiol Aging. 2003 Mar-Apr;24(2):365-78
references.pmid: 12498971
references.citation: Genes Brain Behav. 2006 Mar;5(2):120-30
references.pmid: 16507003
references.citation: Nat Neurosci. 2003 Apr;6(4):345-51
references.pmid: 12658281
references.citation: Neurobiol Dis. 2006 Dec;24(3):475-83
references.pmid: 17008108
references.citation: Neurosci Lett. 1996 Sep 13;215(3):173-6
references.pmid: 8899741
references.citation: Behav Brain Res. 1999 Jul;102(1-2):73-88
references.pmid: 10403017
references.citation: Brain Res Brain Res Rev. 1997 Sep 30;25(1):70-84
references.pmid: 9370051
references.citation: J Biol Chem. 2004 Aug 13;279(33):34873-81
references.pmid: 15190058
references.citation: J Neurochem. 2006 Oct;99(2):438-49
references.pmid: 17029598
references.citation: Science. 2002 Jul 19;297(5580):353-6
references.pmid: 12130773
references.citation: Science. 1992 Apr 10;256(5054):184-5
references.pmid: 1566067
references.citation: Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9382-6
references.pmid: 7937774
references.citation: J Nutr Health Aging. 2006 Jul-Aug;10(4):247-54
references.pmid: 16886094
references.citation: J Biol Chem. 2011 Feb 11;286(6):4454-60
references.pmid: 21148560
references.citation: Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):1989-93
references.pmid: 7892213
references.citation: FASEB J. 2002 Jun;16(8):860-2
references.pmid: 11967228
references.citation: Nat Med. 2003 Apr;9(4):448-52
references.pmid: 12640446
references.citation: Nature. 2002 Apr 4;416(6880):535-9
references.pmid: 11932745
references.citation: Brain Res. 1997 Nov 7;774(1-2):35-43
references.pmid: 9452189
references.citation: Neuromolecular Med. 2003;4(1-2):21-36
references.pmid: 14528050
references.citation: Neurodegener Dis. 2005;2(5):255-60
references.pmid: 16909006
references.citation: Neuron. 2001 Nov 8;32(3):389-401
references.pmid: 11709151
references.citation: Neuron. 2001 Jun;30(3):665-76
references.pmid: 11430801
references.citation: Histol Histopathol. 2009 Jan;24(1):83-100
references.pmid: 19012248
references.citation: Arch Med Res. 2001 Sep-Oct;32(5):367-81
references.pmid: 11578751
references.citation: Acta Neuropathol. 2000 Nov;100(5):580-6
references.pmid: 11045682
references.citation: Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):11065-9
references.pmid: 12920183
references.citation: Curr Alzheimer Res. 2009 Apr;6(2):171-8
references.pmid: 19355852
references.citation: Arch Neurol. 2003 Dec;60(12):1685-91
references.pmid: 14676042
references.citation: Neurosci Lett. 1995 Dec 8;201(2):151-4
references.pmid: 8848240
references.citation: Neurobiol Dis. 2004 Apr;15(3):500-9
references.pmid: 15056457
references.citation: Proc Natl Acad Sci U S A. 1985 Jun;82(12):4245-9
references.pmid: 3159021
references.citation: Science. 2001 Aug 24;293(5534):1487-91
references.pmid: 11520987
references.citation: Am J Pathol. 1994 Jun;144(6):1183-7
references.pmid: 8203459
references.citation: Neurobiol Aging. 1992 Nov-Dec;13(6):641-8
references.pmid: 1362796
references.citation: Science. 2001 Aug 24;293(5534):1491-5
references.pmid: 11520988
references.citation: J Alzheimers Dis. 2005 Feb;7(1):45-61
references.pmid: 15750214
references.citation: Chem Biol. 1997 Feb;4(2):119-25
references.pmid: 9190286
references.citation: J Neurosci. 2003 Aug 6;23(18):6972-81
references.pmid: 12904458
references.citation: Brain Res Brain Res Rev. 2001 Aug;36(1):60-90
references.pmid: 11516773
references.citation: Life Sci. 2006 Nov 2;79(23):2209-16
references.pmid: 16904700
references.citation: Exp Gerontol. 2000 Dec;35(9-10):1363-72
references.pmid: 11113614
references.citation: Eur J Pharmacol. 2004 Apr 19;490(1-3):115-25
references.pmid: 15094078
references.citation: Arch Biochem Biophys. 2009 Jul 1;487(1):59-65
references.pmid: 19454279
references.citation: Neurobiol Aging. 2005 Jul;26(7):1023-8
references.pmid: 15748782
references.citation: Neurosci Lett. 1996 Aug 23;214(2-3):196-8
references.pmid: 8878117
references.citation: Vet J. 2011 Jun;188(3):331-6
references.pmid: 20542455
references.citation: Int J Biochem Cell Biol. 2004 Dec;36(12):2473-90
references.pmid: 15325586
references.citation: Neurobiol Aging. 2000 Jan-Feb;21(1):39-47
references.pmid: 10794847
references.citation: PLoS One. 2009 Jul 22;4(7):e6344
references.pmid: 19623258
references.citation: Annu Rev Physiol. 2002;64:355-405
references.pmid: 11826273
references.citation: Science. 2002 Nov 22;298(5598):1634-6
references.pmid: 12446914
references.citation: PLoS One. 2011 Jan 18;6(1):e14530
references.pmid: 21267079
references.citation: Biochem Biophys Res Commun. 1984 May 16;120(3):885-90
references.pmid: 6375662
references.citation: J Alzheimers Dis. 2004 Aug;6(4):421-31; discussion 443-9
references.pmid: 15345813
references.citation: J Biol Chem. 2001 Oct 12;276(41):37967-73
references.pmid: 11495914
references.citation: Acta Neurobiol Exp (Wars). 2004;64(4):481-9
references.pmid: 15586665
references.citation: Brain Res Bull. 2003 Jun 30;61(1):1-24
references.pmid: 12788204
references.citation: Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1461-5
references.pmid: 1899927
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 6;103(23):8864-9
references.pmid: 16735465
references.citation: Nat Rev Neurosci. 2008 Jul;9(7):532-44
references.pmid: 18568014
references.citation: Behav Pharmacol. 2003 Sep;14(5-6):419-38
references.pmid: 14501255
references.citation: Neuron. 2003 Mar 27;37(6):925-37
references.pmid: 12670422
references.citation: J Neurosci. 2006 Oct 4;26(40):10129-40
references.pmid: 17021169
references.citation: J Neurosci. 2007 Aug 22;27(34):9115-29
references.pmid: 17715348
references.citation: Neurobiol Aging. 1992 Jan-Feb;13(1):99-105
references.pmid: 1542387
references.citation: Brain Res Brain Res Rev. 2000 Aug;33(1):95-130
references.pmid: 10967355
references.citation: Neurobiol Aging. 1993 Sep-Oct;14(5):421-9
references.pmid: 8247224
references.citation: Lab Anim Sci. 1998 Dec;48(6):611-7
references.pmid: 10090085
references.citation: Behav Brain Res. 2009 Jun 8;200(1):117-21
references.pmid: 19162080
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13896-901
references.pmid: 12368474
references.citation: Ann Neurol. 2006 Dec;60(6):729-39
references.pmid: 17192930
references.citation: Neuroreport. 2001 Jul 3;12(9):2007-16
references.pmid: 11435938
references.citation: Nat Cell Biol. 2001 Oct;3(10):905-12
references.pmid: 11584272
references.citation: Neurobiol Aging. 2006 Apr;27(4):570-5
references.pmid: 16481071
references.citation: Neuroscience. 2005;134(4):1285-300
references.pmid: 16039787
references.citation: Reprod Biol Endocrinol. 2004 Jun 16;2:39
references.pmid: 15200672
references.citation: Trends Neurosci. 1992 Sep;15(9):340-5
references.pmid: 1382333
references.citation: J Neurosci. 2003 Oct 1;23(26):8989-9003
references.pmid: 14523101
references.citation: Neurobiol Dis. 2002 Dec;11(3):394-409
references.pmid: 12586549
references.citation: Life Sci. 2002 Oct 11;71(21):2489-98
references.pmid: 12270754
references.citation: NeuroRx. 2005 Jul;2(3):423-37
references.pmid: 16389306
references.citation: EMBO J. 2007 Jul 11;26(13):3169-79
references.pmid: 17581637
references.citation: Science. 1996 Oct 4;274(5284):99-102
references.pmid: 8810256
references.citation: Brain Res Mol Brain Res. 1991 Jul;10(4):299-305
references.pmid: 1656157
references.citation: Trends Mol Med. 2005 Oct;11(10):464-72
references.pmid: 16153892
references.citation: Acta Neuropathol. 2000 Sep;100(3):305-12
references.pmid: 10965801
references.citation: J Neurosci Res. 2006 May 15;83(7):1252-61
references.pmid: 16511867
references.citation: Bioorg Med Chem Lett. 2007 Jan 15;17(2):511-6
references.pmid: 17079141
references.citation: J Mol Neurosci. 2001 Oct;17(2):137-45
references.pmid: 11816787
references.citation: Neurobiol Aging. 2000 Nov-Dec;21(6):905-12
references.pmid: 11124441
references.citation: Neuron. 1995 Feb;14(2):457-66
references.pmid: 7857653
references.citation: Mol Psychiatry. 2002;7(2):132-5
references.pmid: 11840304
references.citation: Science. 2002 Nov 15;298(5597):1379
references.pmid: 12434053
references.citation: Ann Neurol. 1988 Dec;24(6):765-73
references.pmid: 3207359
references.citation: Nat Med. 1996 Jul;2(7):783-7
references.pmid: 8673924
references.citation: J Biol Chem. 2001 Jun 15;276(24):21562-70
references.pmid: 11279122
references.citation: J Neurochem. 2006 Feb;96(4):1005-15
references.pmid: 16412093
references.citation: Nature. 1998 Oct 22;395(6704):755-6
references.pmid: 9796810
references.citation: J Neurosci. 2009 Oct 14;29(41):12994-3005
references.pmid: 19828813
references.citation: Proc Natl Acad Sci U S A. 2000 Mar 14;97(6):2892-7
references.pmid: 10694577
references.citation: Curr Alzheimer Res. 2006 Feb;3(1):71-3
references.pmid: 16472206
references.citation: Neuroscience. 1989;32(3):715-20
references.pmid: 2689908
references.citation: J Neurochem. 2007 Feb;100(3):802-9
references.pmid: 17156133
references.citation: Lancet. 2005 Dec 17;366(9503):2112-7
references.pmid: 16360788
references.citation: Neurology. 1990 Jan;40(1):33-7
references.pmid: 2296379
references.citation: Di Yi Jun Yi Da Xue Xue Bao. 2005 Feb;25(2):168-70, 173
references.pmid: 15698996
references.citation: Neurobiol Aging. 2011 Sep;32(9):1651-61
references.pmid: 19910078
references.citation: Am J Pathol. 1991 Jun;138(6):1423-35
references.pmid: 1905108
references.citation: Psychol Neuropsychiatr Vieil. 2005 Dec;3(4):261-70
references.pmid: 16316817
references.citation: J Neurosci. 2005 Mar 23;25(12):3032-40
references.pmid: 15788759
references.citation: J Exp Anal Behav. 2011 Jan;95(1):109-18
references.pmid: 21541168
references.citation: J Neural Transm (Vienna). 2004 Mar;111(3):347-66
references.pmid: 14991459
references.citation: J Neurochem. 2007 May;101(3):757-70
references.pmid: 17448147
references.citation: Annu Rev Neurosci. 2000;23:155-84
references.pmid: 10845062
references.citation: J Neuropathol Exp Neurol. 2000 Jan;59(1):39-52
references.pmid: 10744034
references.citation: J Neuropathol Exp Neurol. 1999 Sep;58(9):903-20
references.pmid: 10499434
references.citation: Rev Neurosci. 2004;15(5):353-69
references.pmid: 15575491
references.citation: Genes Brain Behav. 2002 Aug;1(3):142-55
references.pmid: 12884970
references.citation: J Neurosci. 2002 Jan 1;22(1):133-41
references.pmid: 11756496
references.citation: Neurobiol Aging. 1994 Mar-Apr;15(2):215-20
references.pmid: 7838294
references.citation: Eur J Neurosci. 2003 Jan;17(2):388-96
references.pmid: 12542676
references.citation: Neuron. 2003 Jul 31;39(3):409-21
references.pmid: 12895417
references.citation: J Neurosci. 2011 May 25;31(21):7691-9
references.pmid: 21613482
references.citation: Acta Neuropathol. 2006 Aug;112(2):175-83
references.pmid: 16775693
references.citation: Nat Genet. 2000 Aug;25(4):402-5
references.pmid: 10932182
references.citation: Nature. 2004 Aug 5;430(7000):631-9
references.pmid: 15295589
references.citation: J Chem Neuroanat. 2003 Nov;26(3):153-69
references.pmid: 14615025