Reduced cortical thickness in hippocampal subregions among cognitively normal apolipoprotein E e4 carriers.
Our objective was to investigate whether asymptomatic carriers of apolipoprotein E epsilon4 [APOE-4] demonstrate pathological differences and atrophy in medial temporal lobe (MTL) subregions. We measured cortical thickness and volume in MTL subregions (hippocampal CA fields 1, 2 and 3; dentate gyrus; entorhinal cortex; subiculum; perirhinal cortex; parahippocampal cortex; and fusiform gyrus) using a high-resolution in-plane (0.4x0.4 mm) MRI sequence in 30 cognitively normal volunteers (14 APOE-4 carriers, 16 non-carriers, mean age 57 years). A cortical unfolding procedure maximized the visibility of this convoluted cortex, providing cortical ribbon thickness measures throughout individual subregions of the hippocampus and surrounding cortex. APOE-4 carriers had reduced cortical thickness compared with non-carriers in entorhinal cortex (ERC) and the subiculum (Sub), but not in the main hippocampal body or perirhinal cortex. Average cortical thickness was 14.8% lower (p=1.0e(- 6)) for ERC and 12.6% lower (p=6.8e(- 5)) for Sub in APOE-4 carriers. Standard volumetric measures of the same regions showed similar, but non-significant trends. Cognitively intact carriers of APOE-4 show regionally specific thinning of the cortical ribbon compared to APOE-3 carriers; cortical thickness may be a more sensitive measure of pathological differences in genetic risk subjects than standard volumetry.
Burggren
A C
AC
David Geffen School of Medicine at UCLA, Center for Cognitive Neurosciences, Semel Institute, 760 Westwood Plaza B8-169, Los Angeles, CA 90095, USA.
Zeineh
M M
MM
Ekstrom
A D
AD
Braskie
M N
MN
Thompson
P M
PM
Small
G W
GW
Bookheimer
S Y
SY
D000483:Alleles; D053327:Apolipoprotein E4 / Q000235:genetics*; D003071:Cognition / Q000502:physiology*; D004192:Discrimination, Psychological / Q000502:physiology; D018728:Entorhinal Cortex / Q000033:anatomy & histology; D005260:Female; D006579:Heterozygote; D006624:Hippocampus / Q000033:anatomy & histology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009483:Neuropsychological Tests
D053327:Apolipoprotein E4