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International Journal of Alzheimer’s Disease
Volume 2011, Article ID 936580, 7 pages
http://dx.doi.org/10.4061/2011/936580
Research Article

Increased mRNA Levels of TCF7L2 and MYC of the Wnt Pathway in Tg-ArcSwe Mice and Alzheimer's Disease Brain

1Section of Molecular Geriatrics, Department of Public Health and Caring Sciences, Uppsala University, 751 85 Uppsala, Sweden
2Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, National Institute of Health, Bethesda, MD 20892-1108, USA
3Department of Experimental Medicine and Public Health, University of Camerino, 62032 Camerino, Italy
4Massachusetts General Hospital, Harvard Medical School, Charlestown, Boston, MA 02119, USA
5Rudbeck Laboratory, Molecular Geriatrics, Dag Hammarskjölds väg 20, 751 85 Uppsala, Sweden

Received 27 October 2010; Accepted 24 November 2010

Academic Editor: Mikko Hiltunen

Copyright © 2011 Elin S. Blom et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Several components in the Wnt pathway, including β-catenin and glycogen synthase kinase 3 beta, have been implied in AD pathogenesis. Here, mRNA brain levels from five-month-old tg-ArcSwe and nontransgenic mice were compared using Affymetrix microarray analysis. With surprisingly small overall changes, Wnt signaling was the most affected pathway with altered expression of nine genes in tg-ArcSwe mice. When analyzing mRNA levels of these genes in human brain, transcription factor 7-like 2 (TCF7L2) and v-myc myelocytomatosis viral oncogene homolog (MYC), were increased in Alzheimer's disease (AD) (P<.05). Furthermore, no clear differences in TCF7L2 and MYC mRNA were found in brains with frontotemporal lobar degeneration, suggesting that altered regulation of these Wnt-related genes could be specific to AD. Finally, mRNA levels of three neurogenesis markers were analyzed. Increased mRNA levels of dihydropyrimidinase-like 3 were observed in AD brain, suggesting that altered Wnt pathway regulation may signify synaptic rearrangement or neurogenesis.