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Science 4 May 2007:
Vol. 316. no. 5825, pp. 750 - 754
DOI: 10.1126/science.1141736
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Reports

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*

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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