This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lambourne, S. L.
Right arrow Articles by Wilkinson, L. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lambourne, S. L.
Right arrow Articles by Wilkinson, L. S.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, January 2005, p. 278-293, Vol. 25, No. 1
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.1.278-293.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Increased tau Phosphorylation on Mitogen-Activated Protein Kinase Consensus Sites and Cognitive Decline in Transgenic Models for Alzheimer's Disease and FTDP-17: Evidence for Distinct Molecular Processes Underlying tau Abnormalities

Sarah L. Lambourne,1 Lynda A. Sellers,1* Toby G. Bush,1 Shewly K. Choudhury,1 Piers C. Emson,1 Yoo-Hun Suh,2 and Lawrence S. Wilkinson1*

Neurobiology Programme, The Babraham Institute, Babraham, Cambridge, United Kingdom,1 Department of Pharmacology, College of Medicine, National Creative Research Initiative Center for Alzheimer's Dementia and Neuroscience Research Institute, MRC, Seoul National University, Seoul, South Korea2

Received 9 June 2004/ Returned for modification 21 June 2004/ Accepted 6 September 2004

Abnormal tau phosphorylation occurs in several neurodegenerative disorders, including Alzheimer's disease (AD) and frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17). Here, we compare mechanisms of tau phosphorylation in mouse models of FTDP-17 and AD. Mice expressing a mutated form of human tau associated with FTDP-17 (tauV337M) showed age-related increases in exogenous tau phosphorylation in the absence of increased activation status of a number of kinases known to phosphorylate tau in vitro. In a "combined" model, expressing both tauV337M and the familial amyloid precursor protein AD mutation APPV717I in a CT100 fragment, age-dependent tau phosphorylation occurred at the same sites and was significantly augmented compared to "single" tauV337M mice. These effects were concomitant with increased activation status of mitogen-activated protein kinase (MAPK) family members (extracellular regulated kinases 1 and 2, p38, and c-Jun NH2-terminal kinase) but not glycogen synthase kinase-3{alpha}ß or cyclin-dependent kinase 5. The increase in MAPK activation was a discrete effect of APPV717I-CT100 transgene expression as near identical changes were observed in single APPV717I-CT100 mice. Age-dependent deficits in memory were also associated with tauV337M and APPV717I-CT100 expression. The data reveal distinct routes to abnormal tau phosphorylation in models of AD and FTDP-17 and suggest that in AD, tau irregularities may be linked to processing of APP C-terminal fragments via specific effects on MAPK activation status.

* Corresponding author. Mailing address: Neurobiology Programme, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom. Phone: 44 1223 496000. Fax: 44 1223 496022. E-mail for Lynda A. Sellers: lynda.sellers@bbsrc.ac.uk. E-mail for Lawrence S. Wilkinson: lawrence.wilkinson{at}bbsrc.ac.uk.

Molecular and Cellular Biology, January 2005, p. 278-293, Vol. 25, No. 1
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.1.278-293.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Lambourne, S. L., Humby, T., Isles, A. R., Emson, P. C., Spillantini, M. G., Wilkinson, L. S. (2007). Impairments in impulse control in mice transgenic for the human FTDP-17 tauV337M mutation are exacerbated by age. Hum Mol Genet 16: 1708-1719 [Abstract] [Full Text]  
  • Li, Z.-g., Zhang, W., Sima, A. A.F. (2007). Alzheimer-Like Changes in Rat Models of Spontaneous Diabetes. Diabetes 56: 1817-1824 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»