THE APOLIPOPROTEIN-E EPSILON-4 ALLELE CAUSES A FASTER DECLINE OF COGNITIVE PERFORMANCES IN DOWNS-SYNDROME SUBJECTS

The apolipoprotein E gene (APOE), located on human chromosome 19, has three common alleles (epsilon 2, epsilon 3, epsilon 4) which encode fo r the three main isoforms indicated as E2, E3 and E4 respectively. Sev eral findings indicate epsilon 4 allele as an importan risk factor in both sporadic and familial late-onset Alzheimer's disease (AD). Pathol ogical 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 de mentia. Aim of this study is to evaluate the possible pathological rol e of epsilon 4 allele as risk factor for developing AD in a DS populat ion. ApoE epsilon 4 allele frequency is not significantly different in DS cases and controls. We found a statistically significant inverse c orrelation between full scale IQ values and age of patients in the sub group 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 (av ailable in 38 patients) showed a faster rate of decline in intellectua l ability in those subjects carrying at least one epsilon 4 allele. Ou r data support the hypothesis that ApoE epsilon 4 allele has a contrib utory role in accelerating the mental deterioration of AD-type in DS p atients. (C) 1997 Elsevier Science B.V.