Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Aug 6;142(3):387-97.
doi: 10.1016/j.cell.2010.06.036. Epub 2010 Jul 22.

Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models

Lars M Ittner  1 , Yazi D Ke, Fabien Delerue, Mian Bi, Amadeus Gladbach, Janet van Eersel, Heidrun Wölfing, Billy C Chieng, MacDonald J Christie, Ian A Napier, Anne Eckert, Matthias Staufenbiel, Edna Hardeman, Jürgen Götz
Affiliations
Free article

Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models

Lars M Ittner et al. Cell. .
Free article

Abstract

Alzheimer's disease (AD) is characterized by amyloid-beta (Abeta) and tau deposition in brain. It has emerged that Abeta toxicity is tau dependent, although mechanistically this link remains unclear. Here, we show that tau, known as axonal protein, has a dendritic function in postsynaptic targeting of the Src kinase Fyn, a substrate of which is the NMDA receptor (NR). Missorting of tau in transgenic mice expressing truncated tau (Deltatau) and absence of tau in tau(-/-) mice both disrupt postsynaptic targeting of Fyn. This uncouples NR-mediated excitotoxicity and hence mitigates Abeta toxicity. Deltatau expression and tau deficiency prevent memory deficits and improve survival in Abeta-forming APP23 mice, a model of AD. These deficits are also fully rescued with a peptide that uncouples the Fyn-mediated interaction of NR and PSD-95 in vivo. Our findings suggest that this dendritic role of tau confers Abeta toxicity at the postsynapse with direct implications for pathogenesis and treatment of AD.

PubMed Disclaimer

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms