Logo eprints

Tau Gene Mutation G389R Causes a Tauopathy with Abundant Pick Body-like Inclusions and Axonal Deposits

Murrell, Jill R. and Spillantini, Maria Grazia and Zolo, Paolo and Guazzelli, Mario and Smith, Michael J. and Hasegawa, Masato and Redi, Francesco and Crowther, R. Anthony and Pietrini, Pietro and Ghetti, Bernardino and Goedert, Michel Tau Gene Mutation G389R Causes a Tauopathy with Abundant Pick Body-like Inclusions and Axonal Deposits. Journal of Neuropathology and Experimental Neurology, 58 (12). pp. 1207-1226. ISSN 0022-3069 (1999)

Full text not available from this repository.


Exonic and intronic mutations in Tau cause familial neurodegenerative syndromes characterized by frontotemporal dementia and dysfunction of multiple cortical and subcortical circuits. Here we describe a G389R mutation in exon 13 of Tau. When 38 years old, the proband presented with progressive aphasia and memory disturbance, followed by apathy, indifference, and hyperphagia. Repeated magnetic resonance imaging showed the dramatic progression of cerebral atrophy. Positron emission tomography revealed marked glucose hypometabolism that was most severe in left frontal, temporal, and parietal cortical regions. Rigidity, pyramidal signs and profound dementia progressed until death at 43 years of age. A paternal uncle, who had died at 43 years of age, had presented with similar symptoms. The proband's brain showed numerous tau-immunoreactive Pick body-like inclusions in the neocortex and the fascia dentata of the hippocampus. In addition, large numbers of tau-positive filamentous inclusions were present in axons in the frontal, temporal, and parietal lobes. Immunoblot analysis of sarkosyl-insoluble tau showed 2 major bands of 60 and 64 kDa. Upon dephosphorylation, these bands resolved into 4 bands consisting of three- and four-repeat tau isoforms. Most isolated tau filaments were straight and resembled filaments found in Alzheimer disease and some frontotemporal dementias with tau mutations. A smaller number of twisted filaments was also observed. Biochemically, recombinant tau proteins with the G389R mutation showed a reduced ability to promote microtubule assembly, suggesting that this may be the primary effect of the mutation. Taken together, the present findings indicate that the G389R mutation in Tau can cause a dementing condition that closely resembles Pick's disease.

Item Type: Article
Identification Number: 10.1097/00005072-199912000-00002
Uncontrolled Keywords: Axonal tau deposits; Brain metabolism; Frontotemporal dementia; Pick body-like inclusions; Tauopathy
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Research Area: Computer Science and Applications
Depositing User: Ms T. Iannizzi
Date Deposited: 13 Apr 2016 09:21
Last Modified: 13 Apr 2016 09:21
URI: http://eprints.imtlucca.it/id/eprint/3442

Actions (login required)

Edit Item Edit Item