In vivo and postmortem clinicoanatomical correlations in frontotemporal dementia and parkinsonism linked to chromosome 17

Bernardino Ghetti, Salvatore Spina, Jill R. Murrell, Edward D. Huey, Pietro Pietrini, Brian Sweeney, Eric M. Wassermann, Catherine Keohane, Martin R. Farlow, Jordan Grafman

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25 Scopus citations

Abstract

Background: Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is associated with mutations in the Microtubule-Associated Protein Tau(MAPT) gene or the Progranulin(PGRN) gene. MAPT mutations lead to widespread deposition of hyperphosphorylated tau protein (FTDP-17T). PGRN mutations are associated with ubiquitin- and TDP-43-positive inclusions in the frontotemporal cortex, striatum and hippocampus (FTDP-17U). Despite the differences, FTDP-17T and FTDP-17U share a largely overlapping clinical phenotype. Objective: To determine whether neuroimaging studies may allow an in vivo early differentiation between FTDP-17T and FTDP-17U. Methods: We studied 25 individuals affected with FTDP-17T associated with either the exon 10+3 (24 subjects) or the G335S (1 subject) MAPT mutation, as well as 3 FTDP-17U individuals, who were carriers of the A9D, IVS6-2A>G or R493X PGRN mutation. Neuroimaging studies, obtained along the course of the disease, were compared to the neuropathologic findings. Results: FTDP-17T cases were associated with symmetric frontotemporal atrophy. Behavioral changes constituted the predominant clinical presentation. Conversely, an asymmetric degenerative process was seen in all 3 PGRN cases, who presented with either corticobasal syndrome (A9D) or frontotemporal dementia and language deterioration (IVS6-2A>G and R493X). Conclusion: Neuroimaging data, in the early disease stage of FTDP-17, may offer the possibility of an early differentiation of FTDP-17T and FTDP-17U phenotypes, independent of the genetic analysis.

Original languageEnglish (US)
Pages (from-to)215-217
Number of pages3
JournalNeurodegenerative Diseases
Volume5
Issue number3-4
DOIs
StatePublished - Mar 1 2008

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Keywords

  • Frontotemporal dementia and parkinsonism linked to chromosome 17
  • Neuropathology
  • Tau
  • TDP-43
  • Ubiquitin

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Ghetti, B., Spina, S., Murrell, J. R., Huey, E. D., Pietrini, P., Sweeney, B., Wassermann, E. M., Keohane, C., Farlow, M. R., & Grafman, J. (2008). In vivo and postmortem clinicoanatomical correlations in frontotemporal dementia and parkinsonism linked to chromosome 17. Neurodegenerative Diseases, 5(3-4), 215-217. https://doi.org/10.1159/000113706