UTILITY OF THE APOLIPOPROTEIN-E GENOTYPE IN THE DIAGNOSIS OF ALZHEIMERS-DISEASE

Background The epsilon 4 allele of the gene encoding apolipoprotein E (APOE) is strongly associated with Alzheimer's disease, but its value in the diagnosis remains uncertain. Methods We reviewed clinical diagn oses and diagnoses obtained at autopsy in 2188 patients referred to 1 of 26 Alzheimer's disease centers for evaluation of dementia. The sens itivity and specificity of the clinical diagnosis or the presence of a n APOE epsilon 4 allele were calculated, with pathologically confirmed Alzheimer's disease used as the standard, The added value of the APOE genotype was estimated with pretest and post-test probabilities from multivariate analyses to gene rare receiver-operating-characteristic c urves plotting sensitivity against the false positive rate. Result's O f the 2188 patients, 1833 were given a clinical diagnosis of Alzheimer 's disease, and The diagnosis was confirmed pathologically in 1770 pat ients at autopsy. Sixty-two percent of patients with clinically diagno sed Alzheimer's disease, as compared with 65 percent of those with pat hologically confirmed Alzheimer's disease, had at least one APOE epsil on 4 allele, The sensitivity of the clinical diagnosis was 93 percent, and the specificity was 55 percent, whereas the sensitivity and speci ficity of the APOE epsilon E4 allele were 65 and 68 percent, respectiv ely. The addition of: information about the APOE genotype increased th e overall specificity to 84 percent in patients who met the clinical c riteria for Alzheimer's disease, although the sensitivity decreased, T he improvement in specificity remained statistically significant in th e multivariate analysis after adjustment for differences in age, clini cal diagnosis, sex, and center. Conclusions APOE genotyping does not p rovide sufficient sensitivity or specificity to be used alone as a dia gnostic test ibr Alzheimer's disease, but when used in combination wit h clinical criteria, it improves the specificity of the diagnosis, (C) 1998, Massachusetts Medical Society.