APOLIPOPROTEIN-E GENOTYPES IN A NEUROPATHOLOGICAL SERIES FROM THE CONSORTIUM TO ESTABLISH A REGISTRY FOR ALZHEIMERS-DISEASE

We evaluated the sensitivity, specificity, and predictive value of the apolipoprotein E (ApoE) epsilon 4 allele for the neuropathological di agnosis of Alzheimer disease (AD) in a clinical series of well-charact erized AD patients and controls followed longitudinally in the multice nter study of the Consortium to Establish a Registry for Alzheimer's D isease (CERAD). In the 162 patients for whom autopsy and ApoE genotype data were available, the clinical diagnosis of AD was verified as the primary cause of dementia in 139 cases (139 of 162, or 86%). The sens itivity and specificity of the epsilon 4 allele for AD were both 83%. The positive predictive value of the epsilon 4 allele was very high at 97% (115 of 119); whereas, the negative predictive value was 44% (19 of 43), providing no useful information for diagnosis of AD when the e psilon 4 allele is not present. Of the cases where AD was not consider ed the primary or sole cause of dementia (n = 23), 6 cases exhibited c oncomitant neuropathological findings of definite or probable AD and 2 of these 6 cases had at least one epsilon 4 allele. These multicenter data extend previous observations reported from smaller case series o f single laboratories and demonstrate that once the clinical diagnosis of AD is established, the presence of an epsilon 4 allele reliably pr edicts the ultimate CERAD neuropathological diagnosis of AD. The findi ngs also suggest that ApoE genotype information is useful clinically i n bolstering diagnostic confidence when an epsilon 4 allele is present and in identifying a group of patients for whom additional diagnostic evaluations may be warranted when the epsilon 4 allele is absent.