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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 2008

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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