Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models.
Cell
; 142(3): 387-97, 2010 Aug 06.
Article
in En
| MEDLINE
| ID: mdl-20655099
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tau Proteins
/
Dendrites
/
Alzheimer Disease
Type of study:
Prognostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
Cell
Year:
2010
Document type:
Article
Affiliation country:
Australia