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Progress in Hereditary Tauopathies: A Mutation in the Tau Gene (G389R) Causes a Pick Disease‐like Syndrome
Author(s) -
GHETTI BERNARDINO,
MURRELL JILL R.,
ZOLO PAOLO,
SPILLANTINI MARIA GRAZIA,
GOEDERT MICHEL
Publication year - 2000
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2000.tb06905.x
Subject(s) - disease , genetics , mutation , gene , biology , medicine , neuroscience , pathology
A bstract : 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 tau immunoreactive. Immunoblot analysis of sarkosyl‐insoluble tau 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.