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


CONCLUSIONS
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.
Ghetti
Bernardino
B
Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, Ind. 46202, USA. bghetti@iupui.edu
Spina
Salvatore
S
Murrell
Jill R
JR
Huey
Edward D
ED
Pietrini
Pietro
P
Sweeney
Brian
B
Wassermann
Eric M
EM
Keohane
Catherine
C
Farlow
Martin R
MR
Grafman
Jordan
J
D001344:Autopsy; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003704:Dementia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007802:Language; D009154:Mutation / Q000235:genetics; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D012189:Retrospective Studies; D013577:Syndrome