title: Modeling Alzheimer's disease with non-transgenic rat models.
abstract: Alzheimer's disease (AD), for which there is no cure, is the most common form of dementia in the elderly. Despite tremendous efforts by the scientific community, the AD drug development pipeline remains extremely limited. Animal models of disease are a cornerstone of any drug development program and should be as relevant as possible to the disease, recapitulating the disease phenotype with high fidelity, to meaningfully contribute to the development of a successful therapeutic agent. Over the past two decades, transgenic models of AD based on the known genetic origins of familial AD have significantly contributed to our understanding of the molecular mechanisms involved in the onset and progression of the disease. These models were extensively used in AD drug development. The numerous reported failures of new treatments for AD in clinical trials indicate that the use of genetic models of AD may not represent the complete picture of AD in humans and that other types of animal models relevant to the sporadic form of the disease, which represents 95% of AD cases, should be developed. In this review, we will discuss the evolution of non-transgenic rat models of AD and how these models may open new avenues for drug development.
authors: The Research Institute of the McGill University Health Centre, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada ; Department of Medicine, McGill University, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada.
authors: Laurent
authors: L
authors: Lecanu
authors: The Research Institute of the McGill University Health Centre, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada ; Department of Medicine, McGill University, Royal Victoria Hospital, 687 Pine avenue West, room L2-05, Montreal H3A 1A1, QC, Canada ; Departments of Biochemistry and Pharmacology and Therapeutics, McGill University, McIntyre Medical Sciences Bldg, 3655 Promenade Sir-William-Osler, room 1325, Montreal Quebec, Canada H3G 1Y6.
authors: Vassilios
authors: V
authors: Papadopoulos
references: J Neural Transm (Vienna). 2011 May;118(5):765-72
references: 21533606
references: Curr Alzheimer Res. 2010 Nov;7(7):602-14
references: 20977411
references: Brain Res. 2011 Jul 11;1400:1-18
references: 21640982
references: J Alzheimers Dis. 2009;17(4):817-25
references: 19542621
references: J Neural Transm (Vienna). 2004 Mar;111(3):367-86
references: 14991460
references: Rejuvenation Res. 2013 Feb;16(1):51-6
references: 23216585
references: Brain Res. 2011 May 4;1388:141-7
references: 21377451
references: J Alzheimers Dis. 2011;25(2):213-7
references: 21368378
references: Behav Brain Res. 1993 Nov 30;57(2):207-13
references: 8117426
references: Mol Med. 2004 Jan-Jun;10(1-6):36-44
references: 15502881
references: Eur J Pharmacol. 2012 Jun 15;685(1-3):74-80
references: 22542664
references: J Alzheimers Dis. 2009;17(1):33-47
references: 19221409
references: Neuroscience. 2010 Jan 20;165(2):427-35
references: 19850110
references: Neurosci Bull. 2011 Apr;27(2):99-106
references: 21441971
references: BMJ. 2005 Aug 6;331(7512):321-7
references: 16081444
references: Mol Neurodegener. 2007 Jun 09;2:11
references: 17559680
references: Environ Toxicol Pharmacol. 2009 Nov;28(3):403-8
references: 21784034
references: Nature. 2000 Jan 13;403(6766):216-20
references: 10646609
references: Chin J Integr Med. 2011 Nov;17(11):847-53
references: 22057414
references: J Alzheimers Dis. 2010;20(1):113-26
references: 20164597
references: J Biol Chem. 2010 Mar 5;285(10):7440-6
references: 20071340
references: BMJ. 1990 Feb 24;300(6723):495-9
references: 2107926
references: Neurobiol Learn Mem. 2011 Mar;95(3):270-6
references: 21144907
references: Nat Genet. 2002 Aug;31(4):391-4
references: 12118252
references: Biochim Biophys Acta. 2001 Jul 27;1537(1):58-62
references: 11476963
references: Brain Res. 2001 Sep 7;912(2):128-36
references: 11532428
references: Neurobiol Learn Mem. 2001 Sep;76(2):125-37
references: 11502145
references: Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003154
references: 15846650
references: Neurosci Lett. 2011 Jan 3;487(1):70-2
references: 20933058
references: Jpn J Pharmacol. 1988 Sep;48(1):121-30
references: 3199599
references: Biochem J. 1994 Aug 1;301 ( Pt 3):871-7
references: 7519852
references: Neuromolecular Med. 2011 Jun;13(2):117-37
references: 21152995
references: Prog Neuropsychopharmacol Biol Psychiatry. 1986;10(3-5):541-51
references: 2879319
references: Prog Brain Res. 1996;109:253-64
references: 9009714
references: J Neurosci. 2001 Aug 1;21(15):5703-14
references: 11466442
references: Life Sci. 1994;55(25-26):2037-49
references: 7997063
references: Exp Brain Res. 2012 Apr;217(3-4):435-40
references: 22006270
references: Am J Pathol. 1980 Dec;101(3 Suppl):S201-11
references: 7006405
references: Lancet Neurol. 2006 May;5(5):388-9
references: 16639835
references: Am J Pathol. 1992 Jun;140(6):1389-99
references: 1376558
references: Am J Pathol. 1980 Dec;101(3 Suppl):S213-9
references: 7457572
references: Eur J Neurosci. 2008 Jul;28(2):239-46
references: 18702695
references: J Alzheimers Dis. 2004 Jun;6(3):209-19
references: 15201476
references: Science. 2001 Aug 24;293(5534):1487-91
references: 11520987
references: Antioxid Redox Signal. 2013 Sep 10;19(8):823-35
references: 23249141
references: BMC Neurosci. 2008 Feb 26;9:28
references: 18302776
references: Biochem Biophys Res Commun. 2010 Apr 30;395(2):207-12
references: 20362550
references: J Pharmacol Exp Ther. 1994 Jul;270(1):319-28
references: 7913497
references: Neurobiol Dis. 2008 Jul;31(1):46-57
references: 18504134
references: Neuron. 1997 Oct;19(4):939-45
references: 9354339
references: Exp Neurol. 1982 May;76(2):441-6
references: 6896495
references: Nature. 1999 Jun 24;399(6738):776-81
references: 10391242
references: Neuroscience. 2009 Dec 15;164(3):1199-209
references: 19733635
references: J Cell Mol Med. 2010 Jun;14(6B):1816-23
references: 19538474
references: Free Radic Biol Med. 2013 Sep;62:90-101
references: 23200807
references: Pharmacol Ther. 1994;63(1):37-122
references: 7972344
references: FEBS Lett. 2006 Jun 26;580(15):3582-8
references: 16753151
references: Neurol Sci. 2001 Feb;22(1):77-8
references: 11487210
references: Pharmacology. 2006;76(1):19-33
references: 16224201
references: Pharmacol Biochem Behav. 1983 Aug;19(2):309-12
references: 6634880
references: Biomark Med. 2012 Aug;6(4):455-76
references: 22917147
references: Expert Opin Investig Drugs. 2009 Mar;18(3):265-76
references: 19243278
references: Neuromolecular Med. 2011 Dec;13(4):223-50
references: 21901428
references: Ann N Y Acad Sci. 1994 Nov 17;738:201-13
references: 7832429
references: J Neurochem. 1993 Nov;61(5):1828-34
references: 8228996
references: Cell Adh Migr. 2011 Jul-Aug;5(4):280-92
references: 21785276
references: Experientia. 1984 Apr 15;40(4):402-3
references: 6714374
references: Br J Psychiatry. 1990 Feb;156:280-1
references: 2317633
references: Biochem Soc Trans. 2011 Aug;39(4):874-80
references: 21787316
references: J Neural Transm (Vienna). 2012 Feb;119(2):173-95
references: 22086139
references: J Neurochem. 2006 Feb;96(4):1005-15
references: 16412093
references: Int J Immunopathol Pharmacol. 2010 Apr-Jun;23(2):589-99
references: 20646354
references: Science. 1971 Apr 16;172(3980):294
references: 5102256
references: Neurosci Lett. 1989 Jul 31;102(2-3):125-30
references: 2682384
references: Proc Natl Acad Sci U S A. 1985 Aug;82(15):5227-30
references: 3860857
references: Eur J Pharmacol. 2011 Apr 25;657(1-3):104-10
references: 21316359
references: J Neurochem. 1986 Apr;46(4):1042-5
references: 3950618
references: Int J Neuropsychopharmacol. 2012 Mar;15(2):223-33
references: 21356140
references: J Neuroendocrinol. 2012 Jan;24(1):93-101
references: 21623958
references: Hum Mol Genet. 2009 Sep 1;18(17):3206-16
references: 19483198
references: Can J Neurol Sci. 1986 Nov;13(4 Suppl):517-20
references: 3791065
references: Prog Neurobiol. 2011 Dec;95(4):547-56
references: 21601614
references: Exp Neurol. 2010 Jun;223(2):267-81
references: 19699201
references: Psychopharmacology (Berl). 1983;81(3):272-3
references: 6417718
references: Neuron. 2003 Jul 31;39(3):409-21
references: 12895417
references: Neurochem Res. 1987 Jul;12(7):613-8
references: 3614511
references: CNS Neurol Disord Drug Targets. 2013 Sep;12(6):870-81
references: 23469836
references: Acta Biochim Pol. 2011;58(4):513-20
references: 22146133
references: Neurobiol Aging. 2009 Jul;30(7):1078-90
references: 18053619
references: Brain Res. 2007 Jan 26;1130(1):206-13
references: 17169350