A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy

Andrew Grover, Elisabet England, Mathew Baker, Naruhiko Sahara, Jennifer Adamson, Brian Granger, Henry Houlden, Ulla Passant, Shu Hui Yen, Michael DeTure, Michael Hutton

Research output: Contribution to journalArticle

45 Scopus citations


A novel mutation in exon 9 of tau, I260V, is associated with a clinical syndrome consistent with frontotemporal dementia with extensive tau pathology; however, neurofibrillary tangles and Pick bodies are absent. Significantly, Sarkosyl-insoluble tau extracted from affected brain tissue consisted almost exclusively of four-repeat isoforms. Consistent with these findings, in vitro biochemical assays demonstrated that the I260V mutation causes a selective increase in tau aggregation and a decrease in tau-induced microtubule assembly with four-repeat isoforms only. The contrasting pathology and biochemical effects of this mutation suggest a different disease mechanism from the other exon 9 mutations and demonstrates the critical role for the first microtubule-binding domain in tau-promoted microtubule assembly and the pathogenic aggregation of tau.

Original languageEnglish (US)
Pages (from-to)131-140
Number of pages10
JournalExperimental Neurology
Issue number1
StatePublished - Nov 2003



  • Aggregation
  • Axonal
  • Dementia
  • Four-repeat
  • Glial tau
  • Isoform
  • Microtubule assembly
  • Neurodegeneration
  • Pick body
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Grover, A., England, E., Baker, M., Sahara, N., Adamson, J., Granger, B., Houlden, H., Passant, U., Yen, S. H., DeTure, M., & Hutton, M. (2003). A novel tau mutation in exon 9 (1260V) causes a four-repeat tauopathy. Experimental Neurology, 184(1), 131-140. https://doi.org/10.1016/S0014-4886(03)00393-5