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

Ittner, Lars M., Ke, Yazi D., Delerue, Fabien, Bi, Mian, Gladbach, Amadeus, van Eersel, Janet, Wolfing, Heidrun, Chieng, Billy C., Christie, MacDonald J., Napier, Ian A., Eckert, Anne, Staufenbiel, Matthias, Hardeman, Edna and Gotz, Jurgen (2010) Dendritic function of tau mediates amyloid-β toxicity in Alzheimer's disease mouse models. Cell, 142 3: 387-397. doi:10.1016/j.cell.2010.06.036


Author Ittner, Lars M.
Ke, Yazi D.
Delerue, Fabien
Bi, Mian
Gladbach, Amadeus
van Eersel, Janet
Wolfing, Heidrun
Chieng, Billy C.
Christie, MacDonald J.
Napier, Ian A.
Eckert, Anne
Staufenbiel, Matthias
Hardeman, Edna
Gotz, Jurgen
Title Dendritic function of tau mediates amyloid-β toxicity in Alzheimer's disease mouse models
Journal name Cell   Check publisher's open access policy
ISSN 0092-8674
1097-4172
Publication date 2010
Sub-type Article (original research)
DOI 10.1016/j.cell.2010.06.036
Open Access Status
Volume 142
Issue 3
Start page 387
End page 397
Total pages 11
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
Abstract Alzheimer's disease (AD) is characterized by amyloid-β (Aβ) and tau deposition in brain. It has emerged that Aβ 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 (Δtau) and absence of tau in tau-/- mice both disrupt postsynaptic targeting of Fyn. This uncouples NR-mediated excitotoxicity and hence mitigates Aβ toxicity. Δtau expression and tau deficiency prevent memory deficits and improve survival in Aβ-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 Aβ toxicity at the postsynapse with direct implications for pathogenesis and treatment of AD.
Keyword HUMDISEASE
MOLNEURO
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Queensland Brain Institute Publications
 
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