Regulation of tau isoform expression and dementia

Biochim Biophys Acta. 2005 Jan 3;1739(2-3):104-15. doi: 10.1016/j.bbadis.2004.08.009.


In the central nervous system (CNS), aberrant changes in tau mRNA splicing and consequently in protein isoform ratios cause abnormal aggregation of tau and neurodegeneration. Pathological tau causes neuronal loss in Alzheimer's disease (AD) and a diverse group of disorders called the frontotemporal dementias (FTD), which are two of the most common forms of dementia and afflict more than 10% of the elderly population. Autosomal dominant mutations in the tau gene cause frontotemporal dementia with parkinsonism-chromosome 17 type (FTDP-17). Just over half the mutations affect tau protein function and decrease its affinity for microtubules (MTs) or increase self-aggregation. The remaining mutations occur within exon 10 (E10) and intron 10 sequences and alter complex regulation of E10 splicing by multiple mechanisms. FTDP-17 splicing mutations disturb the normally balanced levels of distinct protein isoforms that result in altered biochemical and structural properties of tau. In addition to FTDP-17, altered tau isoform levels are also pathogenically associated with other FTD disorders such as progressive supranuclear palsy (PSP), corticobasal degeneration and Pick's disease; however, the mechanisms remain undefined and mutations in tau have not been detected. FTDP-17 highlights the association between splicing mutations and the pronounced variability in pathology as well as phenotype that is characteristic of inherited disorders.

Publication types

  • Review

MeSH terms

  • Alternative Splicing*
  • Base Sequence
  • Dementia / genetics*
  • Gene Expression Regulation*
  • Humans
  • Microtubule-Associated Proteins / genetics
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Nerve Tissue Proteins / genetics
  • Protein Isoforms / genetics
  • Tauopathies / genetics
  • tau Proteins / genetics*


  • MAPT protein, human
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Protein Isoforms
  • tau Proteins