Staging of Alzheimer's pathology in triple transgenic mice: a light and electron microscopic analysis.
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.
Oh
Kwang-Jin
KJ
Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USA.
Perez
Sylvia E
SE
Lagalwar
Sarita
S
Vana
Laurel
L
Binder
Lester
L
Mufson
Elliott J
EJ
Neurobiol Aging. 2008 Sep;29(9):1334-47
17403556
J Neurochem. 2007 Jun;101(5):1172-84
17286590
Neurosci Lett. 1996 Mar 15;206(2-3):189-92
8710183
J Alzheimers Dis. 2005 Sep;8(1):29-41
16155347
Neurosci Lett. 1995 Apr 21;189(3):167-9
7624036
NeuroRx. 2005 Jul;2(3):423-37
16389306
J Neurosci. 2007 Jan 24;27(4):796-807
17251419
Nat Med. 1995 Jul;1(7):693-9
7585153
Neurosci Lett. 2009 Jan 23;450(1):51-5
19022346
J Histochem Cytochem. 1988 May;36(5):547-50
3282007
J Histochem Cytochem. 1993 Apr;41(4):609-16
8450200
J Neurochem. 2007 Jan;100(1):23-35
17116235
J Biol Chem. 2001 Jan 5;276(1):529-34
11013246
Neurobiol Aging. 2003 Dec;24(8):1063-70
14643377
J Alzheimers Dis. 2008 Apr;13(3):295-302
18430997
Brain Pathol. 2007 Jan;17(1):91-103
17493043
Acta Neuropathol. 2000 Sep;100(3):259-69
10965795
Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6923-8
11381127
Brain Res. 2008 Jun 24;1216:92-103
18486110
Eur J Neurosci. 2007 Jan;25(1):59-68
17241267
Neuron. 2005 Mar 3;45(5):675-88
15748844
IUBMB Life. 2007 Apr-May;59(4-5):332-45
17505973
J Neurocytol. 2003 Nov;32(9):1091-105
15044841
Am J Pathol. 2006 Jan;168(1):184-94
16400022
J Neurochem. 1994 Dec;63(6):2279-87
7964748
Behav Genet. 2007 Jan;37(1):79-100
17072762
J Neurosci Res. 1999 Mar 15;55(6):713-23
10220112
Mol Psychiatry. 2004 Jul;9(7):664-83
15052274
J Neurochem. 2006 Mar;96(5):1401-8
16478530
Biochem Biophys Res Commun. 1992 Sep 16;187(2):783-90
1382420
Biochem J. 1994 Aug 1;301 ( Pt 3):871-7
7519852
J Histochem Cytochem. 1989 May;37(5):675-81
2495321
Neurobiol Dis. 2000 Apr;7(2):87-98
10783293
PLoS One. 2008 May 07;3(5):e2124
18461171
Mov Disord. 2005 Aug;20 Suppl 12:S45-52
16092090
J Neurosci Res. 1997 Apr 15;48(2):128-32
9130141
J Neurosci. 2002 Nov 1;22(21):9340-51
12417659
J Biol Chem. 2008 Oct 31;283(44):29639-43
18723507
J Histochem Cytochem. 1985 Jun;33(6):557-63
3889140
Science. 2001 Aug 24;293(5534):1487-91
11520987
Neuroscience. 1994 Sep;62(1):1-13
7816192
J Biol Chem. 1996 Dec 20;271(51):32789-95
8955115
J Histochem Cytochem. 1985 Aug;33(8):845-53
3894502
BMC Neurosci. 2008 Aug 12;9:81
18700006
J Neurosci. 2005 Nov 16;25(46):10637-47
16291936
Acta Neuropathol. 1994;87(6):554-67
7522386
J Neurosci. 2007 Mar 14;27(11):2866-75
17360908
Proc Natl Acad Sci U S A. 1990 Aug;87(15):5827-31
2116006
Neuron. 1994 Oct;13(4):989-1002
7946342
J Biol Chem. 2007 Apr 13;282(15):11590-601
17308309
Neuron. 2004 Aug 5;43(3):321-32
15294141
Biochem J. 2001 May 1;355(Pt 3):869-77
11311152
Neurobiol Dis. 2009 Sep;35(3):415-25
19524671
J Alzheimers Dis. 2007 Dec;12(4):365-75
18198423
Science. 1986 May 2;232(4750):648-50
3083509
J Biol Chem. 2006 Jan 20;281(3):1599-604
16282321
J Comp Neurol. 2009 Jan 1;512(1):27-51
18972553
Neuroscience. 1993 Sep;56(1):109-27
8232910
J Histochem Cytochem. 1988 Sep;36(9):1117-21
2841371
Acta Neuropathol. 1992;84(3):265-72
1384266
Biochim Biophys Acta. 2005 Jan 3;1739(2-3):216-23
15615640
Acta Neuropathol. 2002 Jan;103(1):26-35
11837744
J Neurosci. 2007 Nov 28;27(48):13357-65
18045930
J Neurosci Res. 1994 Dec 15;39(6):669-73
7534834
Nature. 1995 Feb 9;373(6514):523-7
7845465
Eur J Neurosci. 2005 Oct;22(8):1942-50
16262633
Neuron. 2003 Jul 31;39(3):409-21
12895417
FASEB J. 1995 Dec;9(15):1570-6
8529836
J Histochem Cytochem. 1989 Feb;37(2):209-15
2492045
Nat Genet. 2000 Aug;25(4):402-5
10932182