The novel Tau mutation G335S: Clinical, neuropathological and molecular characterization

Salvatore Spina, Jill R. Murrell, Hirotaka Yoshida, Bernardino Ghetti, Niamh Bermingham, Brian Sweeney, Stephen Dlouhy, R. Anthony Crowther, Michel Goedert, Catherine Keohane

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Mutations in Tau cause the inherited neurodegenerative disease, frontotemporal dementia and Parkinsonism linked to chromosome 17 (FTDP-17). Known coding region mutations cluster in the microtubule-binding region, where they alter the ability of tau to promote microtubule assembly. Depending on the tau isoforms, this region consists of three or four imperfect repeats of 31 or 32 amino acids, each of which contains a characteristic and invariant PGGG motif. Here, we report the novel G335S mutation, which changes the PGGG motif of the third tau repeat to PGGS, in an individual who developed social withdrawal, emotional bluntness and stereotypic behavior at age 22, followed by disinhibition, hyperorality and ideomotor apraxia. Abundant tau-positive inclusions were present in neurons and glia in the frontotemporal cortex, hippocampus and brainstem. Sarkosyl-insoluble tau showed paired helical and straight filaments, as well as more irregular rope-like filaments. The pattern of pathological tau bands was like that of Alzheimer disease. Experimentally, the G335S mutation resulted in a greatly reduced ability of tau to promote microtubule assembly, while having no significant effect on heparin-induced assembly of recombinant tau into filaments.

Original languageEnglish
Pages (from-to)461-470
Number of pages10
JournalActa Neuropathologica
Volume113
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Microtubules
Mutation
Aptitude
Ideomotor Apraxia
Frontotemporal Dementia
Chromosomes, Human, Pair 17
Parkinsonian Disorders
Neuroglia
Neurodegenerative Diseases
Brain Stem
Heparin
Hippocampus
Alzheimer Disease
Protein Isoforms
Neurons
Amino Acids
propyl O-beta galactopyranosyl-(1-4)-O-beta galactopyranosyl-(1-4)-alpha galactopyranoside
sarkosyl

Keywords

  • Filament
  • Frontotemporal dementia
  • Microtubule
  • Tau

ASJC Scopus subject areas

  • Clinical Neurology
  • Pathology and Forensic Medicine
  • Neuroscience(all)

Cite this

Spina, S., Murrell, J. R., Yoshida, H., Ghetti, B., Bermingham, N., Sweeney, B., ... Keohane, C. (2007). The novel Tau mutation G335S: Clinical, neuropathological and molecular characterization. Acta Neuropathologica, 113(4), 461-470. https://doi.org/10.1007/s00401-006-0182-5

The novel Tau mutation G335S : Clinical, neuropathological and molecular characterization. / Spina, Salvatore; Murrell, Jill R.; Yoshida, Hirotaka; Ghetti, Bernardino; Bermingham, Niamh; Sweeney, Brian; Dlouhy, Stephen; Crowther, R. Anthony; Goedert, Michel; Keohane, Catherine.

In: Acta Neuropathologica, Vol. 113, No. 4, 04.2007, p. 461-470.

Research output: Contribution to journalArticle

Spina, S, Murrell, JR, Yoshida, H, Ghetti, B, Bermingham, N, Sweeney, B, Dlouhy, S, Crowther, RA, Goedert, M & Keohane, C 2007, 'The novel Tau mutation G335S: Clinical, neuropathological and molecular characterization', Acta Neuropathologica, vol. 113, no. 4, pp. 461-470. https://doi.org/10.1007/s00401-006-0182-5
Spina, Salvatore ; Murrell, Jill R. ; Yoshida, Hirotaka ; Ghetti, Bernardino ; Bermingham, Niamh ; Sweeney, Brian ; Dlouhy, Stephen ; Crowther, R. Anthony ; Goedert, Michel ; Keohane, Catherine. / The novel Tau mutation G335S : Clinical, neuropathological and molecular characterization. In: Acta Neuropathologica. 2007 ; Vol. 113, No. 4. pp. 461-470.
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