Progress in hereditary tauopathies

A mutation in the Tau gene (G389R) causes a pick disease-like syndrome

Bernardino Ghetti, Jill R. Murrell, Paolo Zolo, Maria Grazia Spillantini, Michel Goedert

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We describe the clinical and pathologic phenotypes of the G389R mutation in exon 13 of the Tau gene. Progressive aphasia and memory disturbance are the initial signs and begin in the fourth or fifth decade of life, followed by apathy, indifference, hyperphagia, rigidity, pyramidal signs and dementia. Death occurs after two to five years. Magnetic resonance imaging and neuropathologic studies show frontal and temporal atrophy. Pick body-like and axonal filamentous inclusions found in the neocortex and subcortical white matter, respectively, are tan immunoreactive. Immunoblot analysis of sarkosyl-insoluble tan shows two major bands of 60 and 64 kDa that, upon dephosphorylation, resolve into four bands of three- and four-repeat isoforms. Isolated tau filaments are often straight and occasionally twisted. Recombinant mutant tau protein shows a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. The present findings indicate that the G389R mutation in Tau can cause a dementia similar to that in Pick's disease.

Original languageEnglish
Pages (from-to)52-62
Number of pages11
JournalAnnals of the New York Academy of Sciences
Volume920
StatePublished - 2000

Fingerprint

Pick Disease of the Brain
Tauopathies
tau Proteins
Rigidity
Magnetic resonance imaging
Exons
Protein Isoforms
Genes
Data storage equipment
Mutation
Dementia
Apathy
Hyperphagia
Aptitude
Aphasia
Neocortex
Mutant Proteins
Recombinant Proteins
Microtubules
Atrophy

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Progress in hereditary tauopathies : A mutation in the Tau gene (G389R) causes a pick disease-like syndrome. / Ghetti, Bernardino; Murrell, Jill R.; Zolo, Paolo; Spillantini, Maria Grazia; Goedert, Michel.

In: Annals of the New York Academy of Sciences, Vol. 920, 2000, p. 52-62.

Research output: Contribution to journalArticle

Ghetti, Bernardino ; Murrell, Jill R. ; Zolo, Paolo ; Spillantini, Maria Grazia ; Goedert, Michel. / Progress in hereditary tauopathies : A mutation in the Tau gene (G389R) causes a pick disease-like syndrome. In: Annals of the New York Academy of Sciences. 2000 ; Vol. 920. pp. 52-62.
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