title: Staging of Alzheimer's pathology in triple transgenic mice: a light and electron microscopic analysis.
abstract: The age-related pathological cascade underlying intraneuronal tau formation in 3xTg-AD mice, which harbor the human APP(Swe), PS1(M126V) , and Tau(P301L) gene mutations, remains unclear. At 3 weeks of age, AT180, Alz50, MC1, AT8, and PHF-1 intraneuronal immunoreactivity appeared in the amygdala and hippocampus and at later ages in the cortex of 3xTg-AD mice. AT8 and PHF-1 staining was fixation dependent in young mutant mice. 6E10 staining was seen at all ages. Fluorescent immunomicroscopy revealed CA1 neurons dual stained for 6E10 and Alz50 and single Alz50 immunoreactive neurons in the subiculum at 3 weeks and continuing to 20 months. Although electron microscopy confirmed intraneuronal cytoplasmic Alz50, AT8, and 6E10 reaction product in younger 3xTg-AD mice, straight filaments appeared at 23 months of age in female mice. The present data suggest that other age-related biochemical mechanisms in addition to early intraneuronal accumulation of 6E10 and tau underlie the formation of tau filaments in 3xTg-AD mice.
authors.affiliation: Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Kwang-Jin
authors.initials: KJ
authors.lastname: Oh
authors.forename: Sylvia E
authors.initials: SE
authors.lastname: Perez
authors.forename: Sarita
authors.initials: S
authors.lastname: Lagalwar
authors.forename: Laurel
authors.initials: L
authors.lastname: Vana
authors.forename: Lester
authors.initials: L
authors.lastname: Binder
authors.forename: Elliott J
authors.initials: EJ
authors.lastname: Mufson
references.citation: Neurobiol Aging. 2008 Sep;29(9):1334-47
references.pmid: 17403556
references.citation: J Neurochem. 2007 Jun;101(5):1172-84
references.pmid: 17286590
references.citation: Neurosci Lett. 1996 Mar 15;206(2-3):189-92
references.pmid: 8710183
references.citation: J Alzheimers Dis. 2005 Sep;8(1):29-41
references.pmid: 16155347
references.citation: Neurosci Lett. 1995 Apr 21;189(3):167-9
references.pmid: 7624036
references.citation: NeuroRx. 2005 Jul;2(3):423-37
references.pmid: 16389306
references.citation: J Neurosci. 2007 Jan 24;27(4):796-807
references.pmid: 17251419
references.citation: Nat Med. 1995 Jul;1(7):693-9
references.pmid: 7585153
references.citation: Neurosci Lett. 2009 Jan 23;450(1):51-5
references.pmid: 19022346
references.citation: J Histochem Cytochem. 1988 May;36(5):547-50
references.pmid: 3282007
references.citation: J Histochem Cytochem. 1993 Apr;41(4):609-16
references.pmid: 8450200
references.citation: J Neurochem. 2007 Jan;100(1):23-35
references.pmid: 17116235
references.citation: J Biol Chem. 2001 Jan 5;276(1):529-34
references.pmid: 11013246
references.citation: Neurobiol Aging. 2003 Dec;24(8):1063-70
references.pmid: 14643377
references.citation: J Alzheimers Dis. 2008 Apr;13(3):295-302
references.pmid: 18430997
references.citation: Brain Pathol. 2007 Jan;17(1):91-103
references.pmid: 17493043
references.citation: Acta Neuropathol. 2000 Sep;100(3):259-69
references.pmid: 10965795
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6923-8
references.pmid: 11381127
references.citation: Brain Res. 2008 Jun 24;1216:92-103
references.pmid: 18486110
references.citation: Eur J Neurosci. 2007 Jan;25(1):59-68
references.pmid: 17241267
references.citation: Neuron. 2005 Mar 3;45(5):675-88
references.pmid: 15748844
references.citation: IUBMB Life. 2007 Apr-May;59(4-5):332-45
references.pmid: 17505973
references.citation: J Neurocytol. 2003 Nov;32(9):1091-105
references.pmid: 15044841
references.citation: Am J Pathol. 2006 Jan;168(1):184-94
references.pmid: 16400022
references.citation: J Neurochem. 1994 Dec;63(6):2279-87
references.pmid: 7964748
references.citation: Behav Genet. 2007 Jan;37(1):79-100
references.pmid: 17072762
references.citation: J Neurosci Res. 1999 Mar 15;55(6):713-23
references.pmid: 10220112
references.citation: Mol Psychiatry. 2004 Jul;9(7):664-83
references.pmid: 15052274
references.citation: J Neurochem. 2006 Mar;96(5):1401-8
references.pmid: 16478530
references.citation: Biochem Biophys Res Commun. 1992 Sep 16;187(2):783-90
references.pmid: 1382420
references.citation: Biochem J. 1994 Aug 1;301 ( Pt 3):871-7
references.pmid: 7519852
references.citation: J Histochem Cytochem. 1989 May;37(5):675-81
references.pmid: 2495321
references.citation: Neurobiol Dis. 2000 Apr;7(2):87-98
references.pmid: 10783293
references.citation: PLoS One. 2008 May 07;3(5):e2124
references.pmid: 18461171
references.citation: Mov Disord. 2005 Aug;20 Suppl 12:S45-52
references.pmid: 16092090
references.citation: J Neurosci Res. 1997 Apr 15;48(2):128-32
references.pmid: 9130141
references.citation: J Neurosci. 2002 Nov 1;22(21):9340-51
references.pmid: 12417659
references.citation: J Biol Chem. 2008 Oct 31;283(44):29639-43
references.pmid: 18723507
references.citation: J Histochem Cytochem. 1985 Jun;33(6):557-63
references.pmid: 3889140
references.citation: Science. 2001 Aug 24;293(5534):1487-91
references.pmid: 11520987
references.citation: Neuroscience. 1994 Sep;62(1):1-13
references.pmid: 7816192
references.citation: J Biol Chem. 1996 Dec 20;271(51):32789-95
references.pmid: 8955115
references.citation: J Histochem Cytochem. 1985 Aug;33(8):845-53
references.pmid: 3894502
references.citation: BMC Neurosci. 2008 Aug 12;9:81
references.pmid: 18700006
references.citation: J Neurosci. 2005 Nov 16;25(46):10637-47
references.pmid: 16291936
references.citation: Acta Neuropathol. 1994;87(6):554-67
references.pmid: 7522386
references.citation: J Neurosci. 2007 Mar 14;27(11):2866-75
references.pmid: 17360908
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(15):5827-31
references.pmid: 2116006
references.citation: Neuron. 1994 Oct;13(4):989-1002
references.pmid: 7946342
references.citation: J Biol Chem. 2007 Apr 13;282(15):11590-601
references.pmid: 17308309
references.citation: Neuron. 2004 Aug 5;43(3):321-32
references.pmid: 15294141
references.citation: Biochem J. 2001 May 1;355(Pt 3):869-77
references.pmid: 11311152
references.citation: Neurobiol Dis. 2009 Sep;35(3):415-25
references.pmid: 19524671
references.citation: J Alzheimers Dis. 2007 Dec;12(4):365-75
references.pmid: 18198423
references.citation: Science. 1986 May 2;232(4750):648-50
references.pmid: 3083509
references.citation: J Biol Chem. 2006 Jan 20;281(3):1599-604
references.pmid: 16282321
references.citation: J Comp Neurol. 2009 Jan 1;512(1):27-51
references.pmid: 18972553
references.citation: Neuroscience. 1993 Sep;56(1):109-27
references.pmid: 8232910
references.citation: J Histochem Cytochem. 1988 Sep;36(9):1117-21
references.pmid: 2841371
references.citation: Acta Neuropathol. 1992;84(3):265-72
references.pmid: 1384266
references.citation: Biochim Biophys Acta. 2005 Jan 3;1739(2-3):216-23
references.pmid: 15615640
references.citation: Acta Neuropathol. 2002 Jan;103(1):26-35
references.pmid: 11837744
references.citation: J Neurosci. 2007 Nov 28;27(48):13357-65
references.pmid: 18045930
references.citation: J Neurosci Res. 1994 Dec 15;39(6):669-73
references.pmid: 7534834
references.citation: Nature. 1995 Feb 9;373(6514):523-7
references.pmid: 7845465
references.citation: Eur J Neurosci. 2005 Oct;22(8):1942-50
references.pmid: 16262633
references.citation: Neuron. 2003 Jul 31;39(3):409-21
references.pmid: 12895417
references.citation: FASEB J. 1995 Dec;9(15):1570-6
references.pmid: 8529836
references.citation: J Histochem Cytochem. 1989 Feb;37(2):209-15
references.pmid: 2492045
references.citation: Nat Genet. 2000 Aug;25(4):402-5
references.pmid: 10932182