The apolipoprotein E epsilon 4 allele causes a faster decline of cognitive performances in Down's syndrome subjects

The apolipoprotein E gene (APOE), located on human chromosome 19, has three common alleles (epsilon 2, epsilon 3, epsilon 4) which encode for the three main isoforms indicated as E2, E3 and E4 respectively. Several findings indicate epsilon 4 allele as an importan risk factor in both sporadic and familial late-onset Alzheimer's disease (AD). Pathological changes similar to AD are seen in almost all patients with Down's syndrome (DS) aged over 35 (senile plaques, neurofibrillary tangles and neuronal loss); a proportion of these may subsequently develop dementia. Aim of this study is to evaluate the possible pathological role of epsilon 4 allele as risk factor for developing AD in a DS population. ApoE epsilon 4 allele frequency is not significantly different in DS cases and controls. We found a statistically significant inverse correlation between full scale IQ values and age of patients in the subgroup of DS subjects selected for the presence of at least one epsilon 4 allele, while no correlation was observed in DS subjects with other ApoE genotypes. A longitudinal analysis of cognitive performances (available in 38 patients) showed a faster rate of decline in intellectual ability in those subjects carrying at least one epsilon 4 allele. Our data support the hypothesis that ApoE epsilon 4 allele has a contributory role in accelerating the mental deterioration of AD-type in DS patients. (C) 1997 Elsevier Science B.V.