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.


RESULTS
After neuropathological examination 57 (85%) of 67 of our patients were confirmed as having AD including all 43 who had at least one APOE-epsilon 4 allele. None of the patients found not to have AD carried an epsilon 4 allele. In this series, the specificity of the epsilon 4 allele was 100%, the sensitivity 75%, the positive predictive value 100%, and the negative predictive value 42%. In this necropsy-confirmed series, the epsilon 4/epsilon 4 genotype predicted AD with 100% accuracy. The epsilon 3/epsilon 4 and epsilon 2/epsilon 4 genotypes were also unexpectedly highly specific for AD.


CONCLUSIONS
Data from hundreds of necropsy-confirmed non-AD patients in other longitudinal necropsy series will allow the predictive value of APOE genotypes to be assessed with useful confidence limits.
Saunders
A M
AM
Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina 27710, USA.
Hulette
O
O
Welsh-Bohmer
K A
KA
Schmechel
D E
DE
Crain
B
B
Burke
J R
JR
Alberts
M J
MJ
Strittmatter
W J
WJ
Breitner
J C
JC
Rosenberg
C
C
D000483:Alleles; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001483:Base Sequence; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity
D001057:Apolipoproteins E