Mutations in the tau gene (MAPT) in FTDP-17: The family with Multiple System Tauopathy with Presenile Dementia (MSTD)

Maria Grazia Spillantini, Jill R. Murrell, Michel Goedert, Martin Farlow, Aaron Klug, Bernardino Ghetti

Research output: Contribution to journalArticle

Abstract

Work in 1980s and early 1990s established that the microtubule-associated protein tau is the major component of the paired helical filament of Alzheimer's disease. Similar filamentous deposits are also present in a number of other diseases, including progressive supranuclear palsy, corticobasal degeneration and Pick's disease. In 1998, the relevance of tau dysfunction for the neurodegenerative process became clear, when mutations in the tau gene were found to cause the inherited "frontotemporal dementia and parkinsonism linked to chromosome 17 (ITDP-17)." The paper highlighted here [Spillantini M.G., Murrell J.R., Goedert M., Farlow M., Klug A. and Ghetti B. (1998) Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc. Natl. Acad. Sci. USA 95, 7737-7741] reported a mutation at position +3 in the intron following alternatively spliced exon 10 of the tau gene in a family with abundant filamentous deposits made exclusively of four-repeat tau. Levels of soluble four-repeat tau were increased in individuals with this mutation. It was proposed that the +3 mutation destabilises a stem-loop structure located at the end of exon 10 and the beginning of the intron, thus resulting in an abnormal ratio of three-repeat to four-repeat tau isoforms.

Original languageEnglish
Pages (from-to)373-380
Number of pages8
JournalJournal of Alzheimer's Disease
Volume9
Issue numberSUPPL. 3
StatePublished - 2006

Fingerprint

Frontotemporal Dementia
Mutation
Genes
Introns
Exons
Pick Disease of the Brain
Progressive Supranuclear Palsy
Chromosomes, Human, Pair 17
Microtubule-Associated Proteins
Parkinsonian Disorders
Alzheimer Disease
Protein Isoforms

Keywords

  • Mutation
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology

Cite this

Mutations in the tau gene (MAPT) in FTDP-17 : The family with Multiple System Tauopathy with Presenile Dementia (MSTD). / Spillantini, Maria Grazia; Murrell, Jill R.; Goedert, Michel; Farlow, Martin; Klug, Aaron; Ghetti, Bernardino.

In: Journal of Alzheimer's Disease, Vol. 9, No. SUPPL. 3, 2006, p. 373-380.

Research output: Contribution to journalArticle

Spillantini, Maria Grazia ; Murrell, Jill R. ; Goedert, Michel ; Farlow, Martin ; Klug, Aaron ; Ghetti, Bernardino. / Mutations in the tau gene (MAPT) in FTDP-17 : The family with Multiple System Tauopathy with Presenile Dementia (MSTD). In: Journal of Alzheimer's Disease. 2006 ; Vol. 9, No. SUPPL. 3. pp. 373-380.
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