Effect of apolipoprotein E genotype on Alzheimer's disease neuropathology in a cohort of elderly Norwegians

Abstract

A cohort of elderly Norwegians dying in nursing homes in the Oslo region have been genotyped for the Apolipoprotein E (ApoE) gene. Alzheimer's disease (AD) cortical neuropathology and clinical evidence of dementia were used to assign cases without evidence of other confounding neuropathology. Senile plaque (SP) and neurofibrillary tangle (NFT) densities in frontal, temporal and parietal cortex were then correlated with ApoE genotype to determine any relationship between ApoE genotype and AD pathology. Comparisons with ApoE ε3, ε4 and ε2 allele dosage failed to show any significant effect on cortical SP densities in any cortical area. NFT densities were increased by ε4 allele dosage in the frontal cortex but not in other cortical regions. A reduction was seen in cortical NFT densities with ε2 allele, though again this was not consistently significant in any of the groups. The ε3 allele failed to show any consistent effect on cortical NFT densities. Assessment by individual genotypes showed ε2 3 < ε2 4 < ε3 3 < ε3 4 < ε4 4 which had highest cortical NFT densities in all areas. By genotype, SP densities were generally of the order ε2 4 < ε2 3 < ε3 3 < ε4 4 < ε3 4 though in none of the groups was this significant. Duration of disease showed no consistent effect on neuropathological burden. ApoE genotype may have an effect on determining whether individuals suffer from AD and the age at onset of disease but may only have a minimal effect on pathology burden.