EFFECT OF APOLIPOPROTEIN-E GENOTYPE ON ALZHEIMERS-DISEASE NEUROPATHOLOGY IN A COHORT OF ELDERLY NORWEGIANS

A cohort of elderly Norwegians dying in nursing homes in the Oslo regi on have been genotyped for the Apolipoprotein E (ApoE) gene. Alzheimer 's disease (AD) cortical neuropathology and clinical evidence of demen tia were used to assign cases without evidence of other confounding ne uropathology. Senile plaque (SP) and neurofibrillary tangle (NFT) dens ities in frontal, temporal and parietal cortex were then correlated wi th ApoE genotype to determine any relationship between ApoE genotype a nd AD pathology. Comparisons with ApoE epsilon 3, epsilon 4 and epsilo n 2 allele dosage failed to Show any significant effect on cortical SP densities in any cortical area. NFT densities were increased by epsil on 4 allele dosage in the frontal cortex but not in other cortical reg ions. A reduction was seen in cortical NFT densities with epsilon 2 al lele, though again this was not consistently significant in any of the groups. The epsilon 3 allele failed to show any consistent effect on cortical NFT densities. Assessment by individual genotypes showed epsi lon 2/3 < epsilon 2/4 < epsilon 3/3 < epsilon 3/4 < epsilon 4/4 which had highest cortical NFT densities in all areas. By genotype, SP densi ties were generally of the order epsilon 2/4 < epsilon 2/3 < epsilon 3 /3 < epsilon 4/4 < epsilon 3/4 though in none of the groups was this s ignificant. Duration of disease showed no consistent effect on neuropa thological burden. ApoE genotype may have an effect on determining whe ther individuals suffer from AD and the age at onset of disease but ma y only have a minimal effect on pathology burden.