Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss of APP in Mouse Models.
Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport in the presence or absence of APP. In vivo axonal transport reduced significantly in the absence of functional APP. Overexpression of human wildtype tau maintained normal axonal transport and resulted in a transient compensation of axonal transport deficits in the absence of APP. Mutant R406Wtau in combination with the absence of APP compounded axonal transport deficits and these deficits persisted with age. These results indicate that APP is necessary for axonal transport, and overexpression of human wildtype tau can compensate for the absence of APP at an early age.
Smith
Karen D B
KD
Department of Molecular Physiology and Biophysics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030 USA.
Peethumnongsin
Erica
E
Lin
Han
H
Zheng
Hui
H
Pautler
Robia G
RG
Nature. 1994 Jun 9;369(6480):488-91
8202139
Neuron. 2000 Nov;28(2):461-73
11144356
Neuroimage. 2007;37 Suppl 1:S37-46
17600729
J Cell Biol. 1985 Oct;101(4):1371-8
3930508
EMBO J. 2007 Dec 12;26(24):5143-52
18007595
J Cell Biol. 1999 Sep 20;146(6):1277-88
10491391
J Neurosci. 2005 Mar 2;25(9):2386-95
15745965
Biochim Biophys Acta. 2005 Jan 3;1739(2-3):216-23
15615640
J Neurosci. 2004 May 12;24(19):4657-67
15140937
J Comp Neurol. 2006 Jan 10;494(2):358-67
16320244
Cell Motil Cytoskeleton. 1987;8(3):210-26
2446784
Science. 2006 Nov 3;314(5800):781-4
17082448
Cell. 1995 May 19;81(4):525-31
7758106
Curr Alzheimer Res. 2006 Dec;3(5):437-48
17168643
Neuropathol Appl Neurobiol. 2004 Oct;30(5):491-502
15488025
J Neurosci. 2008 Feb 13;28(7):1682-7
18272688
Trends Mol Med. 2009 Mar;15(3):112-9
19246243
J Biol Chem. 2004 Feb 27;279(9):7893-900
14660557
Nat Rev Neurosci. 2007 Sep;8(9):663-72
17684513
Neuron. 2001 Nov 8;32(3):389-401
11709151
J Cell Sci. 2004 Nov 15;117(Pt 24):5721-9
15537830
FASEB J. 2006 Apr;20(6):762-4
16478768
J Neurosci. 2005 Dec 14;25(50):11542-52
16354912
Cell Mol Life Sci. 2009 Jul;66(14):2299-318
19333550
Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16532-7
17062754
Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13896-901
12368474
Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):6364-9
11959919
Nat Rev Neurosci. 2006 Apr;7(4):278-94
16552414
Neurodegener Dis. 2006;3(3):134-47
16954700
Science. 2007 May 4;316(5825):750-4
17478722
J Neurochem. 2000 Jun;74(6):2583-9
10820221
Neuroimage. 2007 May 1;35(4):1401-8
17369054
Nature. 2001 Dec 6;414(6864):643-8
11740561