High frequency of apolipoprotein E epsilon4 allele in young individuals with very mild Alzheimer's disease-related neurofibrillary changes.

The pathological process of initial neurofibrillary (NF) changes underlying Alzheimer's disease (AD) represents the early preclinical phase of the disease. In a small percentage of individuals, these initial NF changes (Braaks' stage I of six stages) may develop at a surprisingly young age. The aim of this study was to determine the impact of apolipoprotein E (ApoE) on the development of such initial NF changes in young individuals. To this end, the ApoE genotypes were determined using a seminested polymerase chain reaction assay followed by restriction isotyping in young individuals (n = 44; mean age of 38 years) with initial NF changes (stage I). The results were compared with ApoE genotypes of age-matched controls (n = 70) devoid of such changes (stage 0). Stage I cases exhibited a significantly higher epsilon4 allele frequency compared to controls (0.18 vs 0.09, P = 0.039). Thus, the present study reveals an association of epsilon4 allele with the early onset of AD-related NF changes in young individuals. This finding underlines the relevance of the asymptomatic phase in the course of AD.