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Modulation of Tau Subcellular Localization as a Tool to Investigate the Expression of Disease-related Genes
Published on: December 20, 2019
The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing
Amanda J Myers1, Alan M Pittman, Alice S Zhao
1Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, 35 Convent Drive, Bethesda, MD 20892-3707, USA.
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.
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