Presymptomatic generalized brain atrophy in frontotemporal dementia caused by CHMP2B mutation.
OBJECTIVE
CHMP2B mutations are a rare cause of familial frontotemporal dementia (FTD). The clinical syndrome is dominated by personality change and behavioural symptoms, but language, memory, calculation and praxis impairments are also seen early in the course of the disease. There are no detailed studies of brain imaging in CHMP2B mutation-associated FTD. This study aimed to investigate whether there were early or presymptomatic changes in this group of patients.


METHODS
Subjects comprised 16 members of a Danish family with CHMP2B mutation-associated FTD. Nine subjects were presymptomatic mutation carriers with a control group of 7 mutation-negative family members. Volumetric MRI brain scans were performed on all subjects at two time points, and rates of volume change were compared between the two groups.


RESULTS
We demonstrate that generalized atrophy occurs presymptomatically in CHMP2B gene mutation carriers.


CONCLUSIONS
This finding suggests that mutations in CHMP2B have widespread effects throughout the brain, leading to a neuro-anatomical signature distinct from other diseases in the frontotemporal lobar degeneration spectrum.
Rohrer
Jonathan D
JD
Dementia Research Centre, Institute of Neurology, University College, London, UK.
Ahsan
R Laila
RL
Isaacs
Adrian M
AM
Nielsen
Jorgen E
JE
Ostergaard
Leif
L
Scahill
Rachael
R
Warren
Jason D
JD
Rossor
Martin N
MN
Fox
Nick C
NC
Johannsen
Peter
P
D000368:Aged; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D056827:Endosomal Sorting Complexes Required for Transport; D005190:Family; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016875:tau Proteins / Q000502:physiology
C503812:CHMP2B protein, human; D056827:Endosomal Sorting Complexes Required for Transport; D009419:Nerve Tissue Proteins; D016875:tau Proteins