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Science 316 (5825): 750-754

Copyright © 2007 by the American Association for the Advancement of Science

Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model

Erik D. Roberson,1,2* Kimberly Scearce-Levie,1,2 Jorge J. Palop,1,2 Fengrong Yan,1 Irene H. Cheng,1,2 Tiffany Wu,1 Hilary Gerstein,1 Gui-Qiu Yu,1 Lennart Mucke1,2*

Abstract: Many potential treatments for Alzheimer's disease target amyloid-ß peptides (Aß), which are widely presumed to cause the disease. The microtubule-associated protein tau is also involved in the disease, but it is unclear whether treatments aimed at tau could block Aß-induced cognitive impairments. Here, we found that reducing endogenous tau levels prevented behavioral deficits in transgenic mice expressing human amyloid precursor protein, without altering their high Aß levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Aß- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions.

1 Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
2 Department of Neurology, University of California, San Francisco, CA 94158, USA.

* To whom correspondence should be addressed. E-mail: eroberson{at}gladstone.ucsf.edu (E.D.R.); lmucke{at}gladstone.ucsf.edu (L.M.)

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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
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J. Neurosci. 31, 1688-1692
   Abstract »    Full Text »    PDF »
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E. D. Roberson, B. Halabisky, J. W. Yoo, J. Yao, J. Chin, F. Yan, T. Wu, P. Hamto, N. Devidze, G.-Q. Yu, et al. (2011)
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   Abstract »    Full Text »    PDF »
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J. Neurosci. 30, 16419-16428
   Abstract »    Full Text »    PDF »
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J. Neurosci. 30, 16559-16566
   Abstract »    Full Text »    PDF »
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Y. Andrews-Zwilling, N. Bien-Ly, Q. Xu, G. Li, A. Bernardo, S. Y. Yoon, D. Zwilling, T. X. Yan, L. Chen, and Y. Huang (2010)
J. Neurosci. 30, 13707-13717
   Abstract »    Full Text »    PDF »
Tau Reduction Prevents A{beta}-Induced Defects in Axonal Transport.
K. A. Vossel, K. Zhang, J. Brodbeck, A. C. Daub, P. Sharma, S. Finkbeiner, B. Cui, and L. Mucke (2010)
Science 330, 198
   Abstract »    Full Text »    PDF »
A{beta} Oligomers Cause Localized Ca2+ Elevation, Missorting of Endogenous Tau into Dendrites, Tau Phosphorylation, and Destruction of Microtubules and Spines.
H. Zempel, E. Thies, E. Mandelkow, and E.-M. Mandelkow (2010)
J. Neurosci. 30, 11938-11950
   Abstract »    Full Text »    PDF »
Alzheimer Disease: Update on Basic Mechanisms.
X. Bi (2010)
J Am Osteopath Assoc 110, S3-S9
   Abstract »    Full Text »    PDF »
Sodium selenate mitigates tau pathology, neurodegeneration, and functional deficits in Alzheimer's disease models.
J. van Eersel, Y. D. Ke, X. Liu, F. Delerue, J. J. Kril, J. Gotz, and L. M. Ittner (2010)
PNAS 107, 13888-13893
   Abstract »    Full Text »    PDF »
Tau Ser262 phosphorylation is critical for A{beta}42-induced tau toxicity in a transgenic Drosophila model of Alzheimer's disease.
K. Iijima, A. Gatt, and K. Iijima-Ando (2010)
Hum. Mol. Genet. 19, 2947-2957
   Abstract »    Full Text »    PDF »
A Caspase Cleaved Form of Tau Is Preferentially Degraded through the Autophagy Pathway.
P. J. Dolan and G. V. W. Johnson (2010)
J. Biol. Chem. 285, 21978-21987
   Abstract »    Full Text »    PDF »
Tau levels do not influence human ALS or motor neuron degeneration in the SOD1G93A mouse.
I. Taes, A. Goris, R. Lemmens, M. A. van Es, L. H. van den Berg, A. Chio, B. J. Traynor, A. Birve, P. Andersen, A. Slowik, et al. (2010)
Neurology 74, 1687-1693
   Abstract »    Full Text »    PDF »
Molecular mechanisms of neurodegeneration in Alzheimer's disease.
L. Crews and E. Masliah (2010)
Hum. Mol. Genet.
   Abstract »    Full Text »    PDF »
Memory Impairment in Transgenic Alzheimer Mice Requires Cellular Prion Protein.
D. A. Gimbel, H. B. Nygaard, E. E. Coffey, E. C. Gunther, J. Lauren, Z. A. Gimbel, and S. M. Strittmatter (2010)
J. Neurosci. 30, 6367-6374
   Abstract »    Full Text »    PDF »
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J. Coomaraswamy, E. Kilger, H. Wolfing, C. Schafer, S. A. Kaeser, B. M. Wegenast-Braun, J. K. Hefendehl, H. Wolburg, M. Mazzella, J. Ghiso, et al. (2010)
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   Abstract »    Full Text »    PDF »
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M. Cushman, B. S. Johnson, O. D. King, A. D. Gitler, and J. Shorter (2010)
J. Cell Sci. 123, 1191-1201
   Abstract »    Full Text »    PDF »
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process.
B. De Strooper (2010)
Physiol Rev 90, 465-494
   Abstract »    Full Text »    PDF »
{beta}-Amyloid1-42 Gene Transfer Model Exhibits Intraneuronal Amyloid, Gliosis, Tau Phosphorylation, and Neuronal Loss.
G. W. Rebeck, H.-S. Hoe, and C. E.-H. Moussa (2010)
J. Biol. Chem. 285, 7440-7446
   Abstract »    Full Text »    PDF »
Alzheimer A{beta} Peptide Induces Chromosome Mis-Segregation and Aneuploidy, Including Trisomy 21: Requirement for Tau and APP.
A. Granic, J. Padmanabhan, M. Norden, and H. Potter (2010)
Mol. Biol. Cell 21, 511-520
   Abstract »    Full Text »    PDF »
Many Neuronal and Behavioral Impairments in Transgenic Mouse Models of Alzheimer's Disease Are Independent of Caspase Cleavage of the Amyloid Precursor Protein.
J. A. Harris, N. Devidze, B. Halabisky, I. Lo, M. T. Thwin, G.-Q. Yu, D. E. Bredesen, E. Masliah, and L. Mucke (2010)
J. Neurosci. 30, 372-381
   Abstract »    Full Text »    PDF »
Activated Actin-Depolymerizing Factor/Cofilin Sequesters Phosphorylated Microtubule-Associated Protein during the Assembly of Alzheimer-Like Neuritic Cytoskeletal Striations.
I. T. Whiteman, O. L. Gervasio, K. M. Cullen, G. J. Guillemin, E. V. Jeong, P. K. Witting, S. T. Antao, L. S. Minamide, J. R. Bamburg, and C. Goldsbury (2009)
J. Neurosci. 29, 12994-13005
   Abstract »    Full Text »    PDF »
Chemical Manipulation of Hsp70 ATPase Activity Regulates Tau Stability.
U. K. Jinwal, Y. Miyata, J. Koren III, J. R. Jones, J. H. Trotter, L. Chang, J. O'Leary, D. Morgan, D. C. Lee, C. L. Shults, et al. (2009)
J. Neurosci. 29, 12079-12088
   Abstract »    Full Text »    PDF »
Neural stem cells improve cognition via BDNF in a transgenic model of Alzheimer disease.
M. Blurton-Jones, M. Kitazawa, H. Martinez-Coria, N. A. Castello, F.-J. Muller, J. F. Loring, T. R. Yamasaki, W. W. Poon, K. N. Green, and F. M. LaFerla (2009)
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   Abstract »    Full Text »    PDF »
Linking Amyloid and Tau Pathology in Alzheimer's Disease: The Role of Membrane Cholesterol in A{beta}-Mediated Tau Toxicity.
S. Wray and W. Noble (2009)
J. Neurosci. 29, 9665-9667
   Full Text »    PDF »
Caspase-cleaved Tau Expression Induces Mitochondrial Dysfunction in Immortalized Cortical Neurons: IMPLICATIONS FOR THE PATHOGENESIS OF ALZHEIMER DISEASE.
R. A. Quintanilla, T. A. Matthews-Roberson, P. J. Dolan, and G. V. W. Johnson (2009)
J. Biol. Chem. 284, 18754-18766
   Abstract »    Full Text »    PDF »
The Transforming Growth Factor-{beta} Pathway Is a Common Target of Drugs That Prevent Experimental Diabetic Retinopathy.
C. Gerhardinger, Z. Dagher, P. Sebastiani, Y. S. Park, and M. Lorenzi (2009)
Diabetes 58, 1659-1667
   Abstract »    Full Text »    PDF »
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T. G. Bengoechea, Z. Chen, D. A. O'Leary, E. Masliah, and K.-F. Lee (2009)
PNAS 106, 7870-7875
   Abstract »    Full Text »    PDF »
Increased Membrane Cholesterol Might Render Mature Hippocampal Neurons More Susceptible to {beta}-Amyloid-Induced Calpain Activation and Tau Toxicity.
A. M. Nicholson and A. Ferreira (2009)
J. Neurosci. 29, 4640-4651
   Abstract »    Full Text »    PDF »
Tau Mutations in Neurodegenerative Diseases.
M. S. Wolfe (2009)
J. Biol. Chem. 284, 6021-6025
   Abstract »    Full Text »    PDF »
Relevance of Transgenic Mouse Models to Human Alzheimer Disease.
D. A. Morrissette, A. Parachikova, K. N. Green, and F. M. LaFerla (2009)
J. Biol. Chem. 284, 6033-6037
   Abstract »    Full Text »    PDF »
Tau deletion exacerbates the phenotype of Niemann-Pick type C mice and implicates autophagy in pathogenesis.
C. D. Pacheco, M. J. Elrick, and A. P. Lieberman (2009)
Hum. Mol. Genet. 18, 956-965
   Abstract »    Full Text »    PDF »
Amyloid {beta}-Protein Toxicity and the Pathogenesis of Alzheimer Disease.
B. A. Yankner and T. Lu (2009)
J. Biol. Chem. 284, 4755-4759
   Full Text »    PDF »
Neprilysin Overexpression Inhibits Plaque Formation But Fails to Reduce Pathogenic A{beta} Oligomers and Associated Cognitive Deficits in Human Amyloid Precursor Protein Transgenic Mice.
W. J. Meilandt, M. Cisse, K. Ho, T. Wu, L. A. Esposito, K. Scearce-Levie, I. H. Cheng, G.-Q. Yu, and L. Mucke (2009)
J. Neurosci. 29, 1977-1986
   Abstract »    Full Text »    PDF »
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P. J. Crouch, L. W. Hung, P. A. Adlard, M. Cortes, V. Lal, G. Filiz, K. A. Perez, M. Nurjono, A. Caragounis, T. Du, et al. (2009)
PNAS 106, 381-386
   Abstract »    Full Text »    PDF »
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Y. Liu, M.-J. Yoo, A. Savonenko, W. Stirling, D. L. Price, D. R. Borchelt, L. Mamounas, W. E. Lyons, M. E. Blue, and M. K. Lee (2008)
J. Neurosci. 28, 13805-13814
   Abstract »    Full Text »    PDF »
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S. Oddo, A. Caccamo, B. Tseng, D. Cheng, V. Vasilevko, D. H. Cribbs, and F. M. LaFerla (2008)
J. Neurosci. 28, 12163-12175
   Abstract »    Full Text »    PDF »
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K. N. Green, J. S. Steffan, H. Martinez-Coria, X. Sun, S. S. Schreiber, L. M. Thompson, and F. M. LaFerla (2008)
J. Neurosci. 28, 11500-11510
   Abstract »    Full Text »    PDF »
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J. A. Rodriguez-Navarro, A. Gomez, I. Rodal, J. Perucho, A. Martinez, V. Furio, I. Ampuero, M. J. Casarejos, R. M. Solano, J. G. de Yebenes, et al. (2008)
Hum. Mol. Genet. 17, 3128-3143
   Abstract »    Full Text »    PDF »
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G. D. Silverberg, M. Mayo, T. Saul, J. Fellmann, J. Carvalho, and D. McGuire (2008)
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   Abstract »    Full Text »    PDF »
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J. Biol. Chem. 283, 18177-18186
   Abstract »    Full Text »    PDF »
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M. Mapstone, K. Dickerson, and C. J. Duffy (2008)
Brain 131, 1618-1629
   Abstract »    Full Text »    PDF »
Enkephalin Elevations Contribute to Neuronal and Behavioral Impairments in a Transgenic Mouse Model of Alzheimer's Disease.
W. J. Meilandt, G.-Q. Yu, J. Chin, E. D. Roberson, J. J. Palop, T. Wu, K. Scearce-Levie, and L. Mucke (2008)
J. Neurosci. 28, 5007-5017
   Abstract »    Full Text »    PDF »
A Neuronal Microtubule-Interacting Agent, NAPVSIPQ, Reduces Tau Pathology and Enhances Cognitive Function in a Mouse Model of Alzheimer's Disease.
Y. Matsuoka, Y. Jouroukhin, A. J. Gray, L. Ma, C. Hirata-Fukae, H.-F. Li, L. Feng, L. Lecanu, B. R. Walker, E. Planel, et al. (2008)
J. Pharmacol. Exp. Ther. 325, 146-153
   Abstract »    Full Text »    PDF »
Cyclooxygenase-2 inhibition improves amyloid-{beta}-mediated suppression of memory and synaptic plasticity.
L. A. Kotilinek, M. A. Westerman, Q. Wang, K. Panizzon, G. P. Lim, A. Simonyi, S. Lesne, A. Falinska, L. H. Younkin, S. G. Younkin, et al. (2008)
Brain 131, 651-664
   Abstract »    Full Text »    PDF »
The Potential for -Structure in the Repeat Domain of Tau Protein Determines Aggregation, Synaptic Decay, Neuronal Loss, and Coassembly with Endogenous Tau in Inducible Mouse Models of Tauopathy.
M.-M. Mocanu, A. Nissen, K. Eckermann, I. Khlistunova, J. Biernat, D. Drexler, O. Petrova, K. Schonig, H. Bujard, E. Mandelkow, et al. (2008)
J. Neurosci. 28, 737-748
   Abstract »    Full Text »    PDF »
The beta-Propensity of Tau Determines Aggregation and Synaptic Loss in Inducible Mouse Models of Tauopathy.
K. Eckermann, M.-M. Mocanu, I. Khlistunova, J. Biernat, A. Nissen, A. Hofmann, K. Schonig, H. Bujard, A. Haemisch, E. Mandelkow, et al. (2007)
J. Biol. Chem. 282, 31755-31765
   Abstract »    Full Text »    PDF »

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