Regional atrophy of transcallosal prefrontal connections in cognitively normal APOE epsilon4 carriers.
OBJECTIVE
To investigate the possible effect of the APOE epsilon4 allele on age-related regional volume loss within the corpus callosum (CC) in healthy epsilon4 allele carriers compared with noncarriers.


METHODS
A total of 211 subjects, ages 27 to 83 years, 51 epsilon4 carriers and 160 noncarriers underwent T1-weighted MRI scan. All subjects had normal MRI scan and performed within normal range on a neuropsychological battery of tests. CC was segmented into seven functionally relevant regions using a previously published probabilistic map of the CC connectivity. We measured the volumes of the CC and its subregions. We used a regression model (with volumes as dependent and age as independent variables) and compared the slopes between carriers and noncarriers using an analysis of covariance model. We also carried out voxel-based-morphometry analysis to investigate the possible effect of the APOE epsilon4 gene on the gray matter.


RESULTS
We found that the volume of the CC and all subregions decreased with increasing age in both groups. The slope was steeper in the APOE epsilon4 carriers compared withthe noncarriers particularly in the prefrontal region (P = 0.02). No gray matter differences were observed between the two groups.


CONCLUSIONS
APOE epsilon4 polymorphism is associated with accelerated age-related volume loss in the prefrontal callosal tracts without gray matter loss. This result suggests the role of APOE epsilon4 in the brain aging by primarily affecting white matter structures particularly in the frontal lobe.
Filippini
Nicola
N
LENITEM, Laboratory of Epidemiology, Neuroimaging, & Telemedicine- IRCCS S. Giovanni di Dio-FBF, Brescia, Italy.
Zarei
Mojtaba
M
Beckmann
Christian F
CF
Galluzzi
Samantha
S
Borsci
Genoveffa
G
Testa
Cristina
C
Bonetti
Matteo
M
Beltramello
Alberto
A
Ghidoni
Roberta
R
Benussi
Luisa
L
Binetti
Giuliano
G
Frisoni
Giovanni B
GB
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics* / Q000378:metabolism; D001284:Atrophy / Q000473:pathology; D003071:Cognition; D003337:Corpus Callosum / Q000473:pathology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000473:pathology*; D012016:Reference Values
D053327:Apolipoprotein E4