Cortical morphology in children and adolescents with different apolipoprotein E gene polymorphisms: an observational study

Background Alleles of the apolipoprotein E (APOE) gene modulate risk for Alzheimer's disease, with carriers of the epsilon 4 allele being at increased risk and carriers of the epsilon 2 allele possibly at decreased risk compared with non-carriers. Our aim was to determine whether possession of an epsilon 4 allele would confer children with a neural substrate that might render them at risk for Alzheimer's disease, and whether carriers of the epsilon 2 allele might have a so-called protective cortical morphology. Methods 239 healthy children and adolescents were genotyped and had repeated neuroanatomic MRI (total 530 scans). Mixed model regression was used to determine whether the developmental trajectory of the cortex differed by genotype. Findings Cortical thickness of the left entorhinal region was significantly thinner in epsilon 4 carriers than it was in non-epsilon 4 carriers (3 center dot 79 [SE 0 center dot 06] mm, range 1 center dot 54-5 center dot 24 vs 3 center dot 94 [0 center dot 03) mm, 2 center dot 37-6 center dot 11; p=0 center dot 03). There was a significant stepwise increase in cortical thickness in the left entorhinal regions, with epsilon 4 carriers having the thinnest cortex and epsilon 2 carriers the thickest, with epsilon 3 homozygotes occupying an intermediate position (left beta 0 center dot 11 [SE 0 center dot 05], p=0 center dot 02). Neuroanatomic effects seemed fixed and non-progressive, with no evidence of accelerated cortical loss in young healthy epsilon 4 carriers. Interpretation Alleles of the apolipoprotein E gene have distinct neuroanatomic signatures, identifiable in childhood. The thinner entorhinal cortex in individuals with the epsilon 4 allele might contribute to risk of Alzheimer's disease.