Apolipoprotein E (APO E) has been implicated as a significant genetic risk factor in the development of late-onset Alzheimer's disease (AD). The presence of the APO E4 allele appears to have a sex and dosage related effect on the age-of-onset of AD. This observation has been substantiated in several studies.

The fact that many individuals carrying APO E4 alleles do not appear to have any symptoms of AD and that many individuals without APO E4 alleles have symptoms of AD makes the use of this test controversial. Please press here to obtain the current American College of Medical Genetics position statement on the use of APO E testing for AD.

The presence of APO E4 allele(s) in an older individual presenting with symptoms of AD makes this diagnosis more likely. Hence, this molecular diagnostic test can make a significant contribution in the differential diagnosis of AD.

The detection of the three major alleles (APO E2, E3, and E4) can be accurately performed by a direct PCR-based RFLP method. The amino acid polymorphisms resulting in the various APO E types are:
The presence or absence of these amino acids can be detected by the Hha 1 restriction enzyme digestion of PCR products containing these coding sequences. Distinct patterns of restriction fragments result depending on which APO E genotype is present. Examples of these patterns are depicted below for the genotypes: E2/E2, E3/E3, E3/E4, and E4/E4.

The acquisition of patent rights by Athena Diagnostics, Worcester, MA to detect this natural human DNA polymorphism with respect to predictions concerning late-onset Alzheimer's disease prevents CompGene from performing this simple assay.