Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E epsilon 4.
Effects of APOE genotype on age-related slopes of cortical thinning was estimated by measuring the thickness of the cerebral cortex on a point-by-point basis across the cortical mantle in 96 healthy non-demented volunteers aged 48-75 years. Fifty nine were APOE epsilon 4- (no epsilon 4 allele) and 37 were epsilon 4+ (1 or 2 epsilon 4 alleles). The genotype groups had similar age, sex and IQ. Two T(1)-weighted MP-RAGE sequences were averaged for each participant to yield images with high signal-to-noise ratio, and quantified using semi-automated analysis tools. epsilon 4 carriers had thicker cortex than non-carriers in several frontal and temporal areas in both hemispheres, but showed a steeper age-related decline in adjacent areas. Upon comparison of the epsilon 4-specific age-related thinning with previously published patterns of thinning in normal aging and Alzheimer's disease (AD), we conclude that APOE epsilon 4 may function to accelerate thinning in areas found to decline in aging (medial prefrontal and pericentral cortex), but also to initiate thinning in areas associated with AD and amyloid-beta aggregation (occipitotemporal and basal temporal cortex).
Espeseth
Thomas
T
Department of Psychology, University of Oslo, P.O. Box 1094, Blindern, N-0317 Oslo, Norway. thomas.espeseth@psykologi.uio.no
Westlye
Lars T
LT
Fjell
Anders M
AM
Walhovd
Kristine B
KB
Rootwelt
Helge
H
Reinvang
Ivar
I
D000368:Aged; D000375:Aging / Q000473:pathology*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted / Q000379:methods; D016014:Linear Models; D008279:Magnetic Resonance Imaging / Q000379:methods; D008875:Middle Aged
D053327:Apolipoprotein E4