The role of tau (MAPT) in frontotemporal dementia and related tauopathies

R. Rademakers, M. Cruts, C. Van Broeckhoven

Research output: Contribution to journalReview article

223 Scopus citations

Abstract

Tau is a multifunctional protein that was originally identified as a microtubule-associated protein. In patients diagnosed with frontotemporal dementia and parkinsonism linked to chromosome 17, mutations in the gene encoding tau (MAPT) have been identified that disrupt the normal binding of tau to tubulin resulting in pathological deposits of hyperphosphorylated tau. Abnormal filamentous tau deposits have been reported as a pathological characteristic in several other neurodegenerative diseases, including frontotemporal dementia, Pick Disease, Alzheimer disease, argyrophilic grain disease, progressive supranuclear palsy, and corticobasal degeneration. In the last five years, extensive research has identified 34 different pathogenic MAPT mutations in 101 families worldwide. In vitro, cell-free and transfected cell studies have provided valuable information on tau dysfunction and transgenic mice carrying human MAPT mutations are being generated to study the influence of MAPT mutations in vivo. This mutation update describes the considerable differences in clinical and pathological presentation of patients with MAPT mutations and summarizes the effect of the different mutations on tau functioning. In addition, the role of tau as a genetic susceptibility factor is discussed, together with the genetic evidence for additional causal genes for tau-positive as well as tau-negative dementia.

Original languageEnglish (US)
Pages (from-to)277-295
Number of pages19
JournalHuman mutation
Volume24
Issue number4
DOIs
StatePublished - Oct 19 2004

Keywords

  • Alzheimer
  • Frontotemporal dementia
  • Linkage
  • MAPT
  • Microtubule
  • Pick
  • Tau

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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