The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts

Amanda J Myers, Alan M. Pittman, Alice S. Zhao, Kristen Rohrer, Mona Kaleem, Lauren Marlowe, Andrew Lees, Doris Leung, Ian G. McKeith, Robert H. Perry, Chris M. Morris, John Q. Trojanowski, Christopher Clark, Jason Karlawish, Steve Arnold, Mark S. Forman, Vivianna Van Deerlin, Rohan de Silva, John Hardy

Research output: Contribution to journalArticle

189 Scopus citations

Abstract

Previously we have shown that the H1c haplotype on the background of the H1 clade of haplotypes at the MAPT locus is associated with increased risk for progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and Alzheimer's disease (AD). Here we replicated the association with AD in an additional autopsy confirmed series. We show that this haplotype increases both the expression of total MAPT transcript as well as specifically increasing the proportion of 4 microtubule binding repeat containing transcripts. We discuss these findings both in terms of the problems facing the dissection of the etiologies of complex traits and the pathogenesis of the tauopathies.

Original languageEnglish
Pages (from-to)561-570
Number of pages10
JournalNeurobiology of Disease
Volume25
Issue number3
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Neurology

Cite this

Myers, A. J., Pittman, A. M., Zhao, A. S., Rohrer, K., Kaleem, M., Marlowe, L., Lees, A., Leung, D., McKeith, I. G., Perry, R. H., Morris, C. M., Trojanowski, J. Q., Clark, C., Karlawish, J., Arnold, S., Forman, M. S., Van Deerlin, V., de Silva, R., & Hardy, J. (2007). The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts. Neurobiology of Disease, 25(3), 561-570. https://doi.org/10.1016/j.nbd.2006.10.018