THE APOLIPOPROTEIN-E-EPSILON-4 ALLELE IS A RISK FACTOR FOR ALZHEIMERS-DISEASE OF EARLY AND LATE-ONSET

The apolipoprotein E genotype was determined in 50 patients with clini cally diagnosed and prospectively confirmed Alzheimer's disease of mil d to moderate severity and in 50 healthy age- and sex-matched controls . The frequency of the epsilon4 allele was increased in the patients i rrespective of the age at onset and of a possible familial transmissio n of the disease. It was associated with a relative risk of 2.97. In p atients who experienced first symptoms after the age of 65 years there was an inverse correlation between the number of epsilon4 alleles and age at onset. The results suggest that in the absence of amyloid prec ursor protein mutations and of a gene which has not yet been precisely localized on chromosome 14, apolipoprotein E is involved in the patho genesis of Alzheimer's disease. It probably exerts its influence by an acceleration or retardation of amyloid formation and/or tau hyperphos phorylation.