Gene & Protein Tests
Apolipoprotein E
Several recent studies show that the natural variations of the gene for apolipoprotein E (APOE) correlate surprisingly well with risk of Alzheimer's disease.
The APOE gene, located on chromosome 19, comes in three varieties, called alleles (al-EELS). They are designated with a lower-case "e": e2, e3, and e4. Everyone's APOE gene has two of these three alleles, so there are six possible combinations in any individual's DNA. The e2 allele is associated with decreased risk of Alzheimer's disease. The e3 allele is associated with average risk. Even one e4 allele approximately doubles risk, while two e4 alleles boost risk eight- to tenfold.
Scientists have long been aware of the APOE gene and the protein it instructs the body to make, apoE, because the protein plays a role in the metabolism of cholesterol, a key risk factor for heart disease. Recently, researchers discovered that apoE also binds to amyloid, a substance associated with the senile plaques of Alzheimer's. The gene's various alleles affect amyloid differently. The e4 allele appears to increase deposition of amyloid in the brain. The mechanism remains a mystery, but is the focus of a great deal of research.
Genetic testing for APOE alleles is currently possible, but it is not widely available because it only suggests increased risk; it does not predict development of Alzheimer's. But one day, researchers hope, drugs will be able to prevent development of Alzheimer's disease in those who are at high risk. At that point APOE testing would make more sense.
Tau protein and beta-amyloid42
Both tau protein and beta-amyloid42 are proteins that appear in cerebrospinal fluid, the fluid that surrounds the brain and spinal cord. Doctors can sample cerebrospinal fluid by performing a lumbar puncture, popularly known as a spinal tap.
Compared with those whose brains function normally, people with Alzheimer's disease have unusually high levels of tau protein (more than 420 picograms/mL) and unusually low levels of beta-amyloid42 (less than 1,240 picograms/mL).
These biochemical markers have become the basis for a new test for Alzheimer's disease, ADmark Assays, from Athena Neurosciences, Inc. The company claims that in people over 60 years of age, the two-protein test can diagnose or rule out Alzheimer's disease with up to 95% accuracy.
Experts caution, however, that the test is not definitively diagnostic, and that despite the manufacturer's claims, it has not been in use long enough to have a track record. Nonetheless, it is a potentially exciting development in Alzheimer's disease testing.
According to a report in Patient Care (Nov. 15, 1996), the two-protein test costs $390 beyond the cost of the lumbar puncture. Medicare approval is pending.