%L eprints3075
%D 2008
%X 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.
%A Bernardino Ghetti
%A Salvatore Spina
%A Jill R. Murrell
%A Edward D Huey
%A Pietro Pietrini
%A B. Sweeney
%A Eric M. Wassermann
%A C. Keohane
%A M.R. Farlow
%A Jordan Grafman
%R 10.1159/000113706
%J Neurodegenerative Diseases
%N 3-4
%T In vivo and Postmortem Clinicoanatomical Correlations in Frontotemporal Dementia and Parkinsonism Linked to Chromosome 17
%P 215-217
%V 5
%I Karger
%O Free access from publisher's website