Accelerated age-related cortical thinning in healthy carriers of apolipoprotein E epsilon 4

Neurobiol Aging. 2008 Mar;29(3):329-40. doi: 10.1016/j.neurobiolaging.2006.10.030. Epub 2006 Dec 11.


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).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aging / pathology*
  • Apolipoprotein E4 / genetics*
  • Brain Mapping*
  • Cerebral Cortex / pathology*
  • Humans
  • Image Processing, Computer-Assisted / methods
  • Linear Models
  • Magnetic Resonance Imaging / methods
  • Middle Aged


  • Apolipoprotein E4