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

doi:10.1126/science.1141736

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

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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-ßpeptides (Aß), which are widely presumed to causethe disease. The microtubule-associated protein tau is alsoinvolved in the disease, but it is unclear whether treatmentsaimed at tau could block Aß-induced cognitive impairments.Here, we found that reducing endogenous tau levels preventedbehavioral deficits in transgenic mice expressing human amyloidprecursor protein, without altering their high Aßlevels. Tau reduction also protected both transgenic and nontransgenicmice against excitotoxicity. Thus, tau reduction can block Aß-and excitotoxin-induced neuronal dysfunction and may representan effective strategy for treating Alzheimer's disease and relatedconditions.

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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