Voxel-based morphometry in frontotemporal lobar degeneration with ubiquitin-positive inclusions with and without progranulin mutations.
BACKGROUND
Mutations in the progranulin gene (PGRN) have recently been identified as a cause of frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) in some families.


OBJECTIVE
To determine whether there is a difference in the patterns of atrophy in FTLD-U cases with and without PGRN mutations.


METHODS
Case-control study.


METHODS
Brain bank of a tertiary care medical center. Patients Eight subjects who had screened positive for PGRN mutations (PGRN-positive) and who underwent volumetric magnetic resonance imaging were identified. Subjects were then matched by clinical diagnosis to a group of 8 subjects with a pathological diagnosis of FTLD-U who had screened negative for PGRN mutations (PGRN-negative). All subjects were then age-matched and sex-matched to a control subject.


METHODS
Voxel-based morphometry was used to assess the patterns of gray matter atrophy in the PGRN-positive group compared with the PGRN-negative group and compared with controls.


RESULTS
The PGRN-positive group showed a widespread and severe pattern of gray matter loss predominantly affecting the frontal, temporal, and parietal lobes. The PGRN-negative group showed a less severe pattern of gray matter loss restricted mainly to the temporal and frontal lobes. On direct comparison, the PGRN-positive group showed greater gray matter loss in the frontal and parietal lobes compared with the PGRN-negative group.


CONCLUSIONS
Findings from this study suggest that PGRN mutations may be associated with a specific and severe pattern of cerebral atrophy in subjects with FTLD-U.
Whitwell
Jennifer L
JL
Division of Behavioral Neurology, Department of Neurology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
Jack
Clifford R
CR
Baker
Matthew
M
Rademakers
Rosa
R
Adamson
Jennifer
J
Boeve
Bradley F
BF
Knopman
David S
DS
Parisi
Joseph F
JF
Petersen
Ronald C
RC
Dickson
Dennis W
DW
Hutton
Michael L
ML
Josephs
Keith A
KA
D000368:Aged; D001931:Brain Mapping; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D003704:Dementia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000077153:Progranulins; D025801:Ubiquitin / Q000378:metabolism*
C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D025801:Ubiquitin