[The apolipoprotein E-epsilon 4 allele is a risk factor for Alzheimer disease with early and late onset]

The apolipoprotein E genotype was determined in 50 patients with clinically diagnosed and prospectively confirmed Alzheimer's disease of mild to moderate severity and in 50 healthy age- and sex-matched controls. The frequency of the epsilon 4 allele was increased in the patients irrespective of the age at onset and of a possible familial transmission of the disease. It was associated with a relative risk of 2.97. In patients who experienced first symptoms after the age of 65 years there was an inverse correlation between the number of epsilon 4 alleles and age at onset. The results suggest that in the absence of amyloid precursor protein mutations and of a gene which has not yet been precisely localized on chromosome 14, apolipoprotein E is involved in the pathogenesis of Alzheimer's disease. It probably exerts its influence by an acceleration or retardation of amyloid formation and/or tau hyperphosphorylation.