The absence of an apolipoprotein epsilon 4 allele is associated with a more aggressive form of Alzheimer's disease

We investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE epsilon 4 allele. The rate of decline in modified Mini-Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE epsilon 4 alleles compared with patients with other genotypes. Compared with patients without an APOE epsilon 4 allele, the risk of mortality was also decreased in patients with at least one epsilon 4 allele (RR = 0.38; CI = 0.17-0.84, p < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE epsilon 4 is associated with a less aggressive form of AD.