Specificity, sensitivity, and predictive value of apolipoprotein-E genotyping for sporadic Alzheimer's disease

Background We aimed to determine the specificity, sensitivity, and predictive value of apolipoprotein E(APOE) genotyping in 67 consecutive Patients with clinical diagnoses of sporadic Alzheimer's disease (AD) who underwent necropsy. Methods We studied patients who attended the Duke Memory Disorders Clinic and were diagnosed as having probable AD. These patients were followed up until they died, APOE genotyping was done during life in most cases, but in some brain tissue obtained at necropsy was used. Members of known AD families were excluded. Findings After neuropathological examination 57 (85%) of 67 of our patients were confirmed as having AD including all 43 who had at least one APOE-is an element of 4 allele. None of the patients found not to have AD carried an is an element of 4 allele, In this series, the specificity of the is an element of 4 allele was 100%, the sensitivity 75%, the positive predictive value 100%, and the negative predictive value 42%. In this necropsy-confirmed series, the is an element of 4/is an element of 4 genotype predicted AD with 100% accuracy. The is an element of 3/is an element of 4 and is an element of 2/is an element of 4 genotypes were also unexpectedly highly specific for AD. Interpretation Data from hundreds of necropsy-confirmed non-AD patients in other longitudinal necropsy series will allow the predictive value oi APOE genotypes to be assessed with useful confidence limits.