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

Ittner, Lars M. and Ke, Yazi D. and Delerue, Fabien and Bi, Mian and Gladbach, Amadeus and van Eersel, Janet and Wölfing, Heidrun and Chieng, Billy C. and Christie, MacDonald J. and Napier, Ian A. and Eckert, Anne and Staufenbiel, Matthias and Hardeman, Edna and Götz, Jürgen. (2010) Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell, Vol. 142, H. 3. pp. 387-397.

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Official URL: http://edoc.unibas.ch/dok/A6006413

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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.
Faculties and Departments:03 Faculty of Medicine > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Psychiatrie (Klinik) > Erwachsenenpsychiatrie UPK > Erwachsenenpsychiatrie (Lang)
UniBasel Contributors:Eckert, Anne
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Cell Press
ISSN:0092-8674
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:07 Dec 2012 13:03
Deposited On:07 Dec 2012 13:02

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