Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Genetics

The MAPT locus—a genetic paradigm in disease susceptibility

Understanding how genetic variation can confer susceptibility to neurological disease is an urgent priority. A new gene-expression study has explored the relationship between DNA sequence variation at the microtubule-associated protein tau (MAPT) locus and MAPT expression in the brain, providing an exciting new paradigm for the field.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: The MAPT gene locus and the tau protein isoforms.

References

  1. Trabzuni, D. et al. MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies. Hum. Mol. Genet. http://dx.doi.org/10.1093/hmg/dds238.

  2. Caffrey, T. M., Joachim, C., Paracchini, S., Esiri, M. M. & Wade-Martins, R. Haplotype-specific expression of exon 10 at the human MAPT locus. Hum. Mol. Genet. 15, 3529–3537 (2006).

    Article  CAS  PubMed Central  Google Scholar 

  3. Caffrey, T. M., Joachim, C. & Wade-Martins, R. Haplotype-specific expression of the N-terminal exons 2 and 3 at the human MAPT locus. Neurobiol. Aging 29, 1923–1929 (2008).

    Article  CAS  PubMed Central  Google Scholar 

  4. Höglinger, G. U. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699–705 (2011).

    Article  PubMed Central  Google Scholar 

  5. Myers, A. J. et al. The MAPT H1c risk haplotype is associated with increased expression of tau and especially of 4 repeat containing transcripts. Neurobiol. Dis. 25, 561–570 (2007).

    Article  CAS  Google Scholar 

  6. Stefansson, H. et al. A common inversion under selection in Europeans. Nat. Genet. 37, 129–137 (2005).

    Article  CAS  Google Scholar 

  7. Panda, D., Samuel, J. C., Massie, M., Feinstein, S. C. & Wilson, L. Differential regulation of microtubule dynamics by three- and four-repeat tau: implications for the onset of neurodegenerative disease. Proc. Natl Acad. Sci. USA 100, 9548–9553 (2003).

    Article  CAS  PubMed Central  Google Scholar 

  8. Dixit, R., Ross, J. L., Goldman, Y. E. & Holzbaur, E. L. Differential regulation of dynein and kinesin motor proteins by tau. Science 319, 1086–1089 (2008).

    Article  CAS  PubMed Central  Google Scholar 

  9. Zhong, Q., Congdon, E. E., Nagaraja, H. N. & Kuret, J. Tau isoform composition influences the rate and extent of filament formation. J. Biol. Chem. 287, 20711–20719 (2012).

    Article  CAS  PubMed Central  Google Scholar 

  10. Ittner, L. M. et al. Dendritic function of tau mediates amyloid-β toxicity in Alzheimer's disease mouse models. Cell 142, 387–397 (2010).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Work in the Wade-Martins laboratory has been supported by Alzheimer's Research UK, Cure PSP, The Wellcome Trust and the Monument Trust Discovery Award from Parkinson's UK.

Author information

Authors and Affiliations

Authors

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Wade-Martins, R. The MAPT locus—a genetic paradigm in disease susceptibility. Nat Rev Neurol 8, 477–478 (2012). https://doi.org/10.1038/nrneurol.2012.169

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2012.169

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing