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

Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
Science (Impact Factor: 33.61). 06/2007; 316(5825):750-4. DOI: 10.1126/science.1141736
Source: PubMed


Many potential treatments for Alzheimer's disease target amyloid-beta peptides (Abeta), 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 Abeta-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 Abeta levels. Tau reduction also protected both transgenic and nontransgenic mice against excitotoxicity. Thus, tau reduction can block Abeta- and excitotoxin-induced neuronal dysfunction and may represent an effective strategy for treating Alzheimer's disease and related conditions.

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    • "First, tau-deficient neurons have been shown to be resistant to Aβ-mediated neurotoxicity (Rapoport et al., 2002). Second, genetic deficiency of tau in an AD mouse model improved cognitive function and reduced excitotoxic injury (Roberson et al., 2007; Ittner et al., 2010). Third, Shipton and colleagues recently showed that deficiency of tau protected against Aβ-induced impairment of long-term potentiation in hippocampal slices of wild type mice (Shipton et al., 2011). "
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