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

Summary Background Alleles of the apolipoprotein E (APOE) gene modulate risk for Alzheimer's disease, with carriers of the ε4 allele being at increased risk and carriers of the ε2 allele possibly at decreased risk compared with non-carriers. Our aim was to determine whether possession of an ε4 allele would confer children with a neural substrate that might render them at risk for Alzheimer's disease, and whether carriers of the ε2 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 ε4 carriers than it was in non-ε4 carriers (3·79 [SE 0·06] mm, range 1·54–5·24 vs 3·94 [0·03] mm, 2·37–6·11; p=0·03). There was a significant stepwise increase in cortical thickness in the left entorhinal regions, with ε4 carriers having the thinnest cortex and ε2 carriers the thickest, with ε3 homozygotes occupying an intermediate position (left β 0·11 [SE 0·05], p=0·02). Neuroanatomic effects seemed fixed and non-progressive, with no evidence of accelerated cortical loss in young healthy ε4 carriers. Interpretation Alleles of the apolipoprotein E gene have distinct neuroanatomic signatures, identifiable in childhood. The thinner entorhinal cortex in individuals with the ε4 allele might contribute to risk of Alzheimer's disease.