Sodium selenate mitigates tau pathology, neurodegeneration, and functional deficits in Alzheimer's disease models

Janet van Eersel, Yazi D. Ke, Xin Liu, Fabien Delerue, Jillian J. Kril, Jürgen Götz*, Lars M. Ittner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

189 Citations (Scopus)


Alzheimer's disease (AD) brains are characterized by amyloid-β- containing plaques and hyperphosphorylated tau-containing neurofibrillary tangles (NFTs); however, in frontotemporal dementia, the tau pathology manifests in the absence of overt amyloid-β plaques. Therapeutic strategies so far have primarily been targeting amyloid-β, although those targeting tau are only slowly beginning to emerge. Here, we identify sodium selenate as a compound that reduces tau phosphorylation both in vitro and in vivo. Importantly, chronic oral treatment of two independent tau transgenic mouse strains with NFT pathology, P301L mutant pR5 and K369I mutant K3 mice, reduces tau hyperphosphorylation and completely abrogates NFT formation. Furthermore, treatment improves contextual memory and motor performance, and prevents neurodegeneration. As hyperphosphorylation of tau precedes NFT formation, the effect of selenate on tau phosphorylation was assessed in more detail, a process regulated by both kinases and phosphatases. A major phosphatase implicated in tau dephosphorylation is the serine/threonine-specific protein phosphatase 2A (PP2A) that is reduced in both levels and activity in the AD brain. We found that selenate stabilizes PP2A-tau complexes. Moreover, there was an absence of therapeutic effects in sodium selenate-treated tau transgenic mice that coexpress a dominant-negative mutant form of PP2A, suggesting amediating role for PP2A. Taken together, sodium selenate mitigates tau pathology in several AD models, making it a promising lead compound for tau-targeted treatments of AD and related dementias.

Original languageEnglish
Pages (from-to)13888-13893
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
Publication statusPublished - 3 Aug 2010
Externally publishedYes


  • Frontotemporal lobar degeneration
  • Neurofibrillary tangle
  • Protein phosphatase 2A
  • Transgenic
  • Treatment

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