Alzheimer’s disease is said to be the most feared disease in the world. It robs a person of their ability to have a productive and meaningful relationship with the world, and puts a financial and emotional strain on loved ones. Unfortunately, there is currently no proven way to prevent or cure Alzheimer disease. Considering all of this information, is there a role for genetic testing to predict risk?
The gene at the forefront of this discussion is APOE, which is a susceptibility gene. This means that if a person inherits a certain variant, s/he will be at increased risk to develop the disorder, but it is not a certainty. It is only more likely because they are genetically more susceptible. Like most genes, everyone inherits 2 copies of the APOE gene – 1 from each parent. There are 3 common variations of this gene - APOE 2, 3, and 4. APOE 2 is suspected to be somewhat protective against Alzheimer’s disease and might lower risk. APOE 3 is neutral in that it does not increase or decrease risk; it is also the most common variant in the population. APOE 4 is the allele (or variation) associated with an increased risk of developing Alzheimer’s. Because we have 2 copies, there are 6 possible combinations a person can inherit – 2/2, 2/3, 3/3, ¾, 2/4, and 4/4. About 25% of the population has at least 1 APOE 4 variant. Those who are 3/4 have up to about a 40% chance to develop Alzheimer disease. However, in terms of risk, inheriting 2 copies of APOE 4 is worse than 1 copy and those who are 4/4 have up to an 87% chance to develop Alzheimer disease.Routine testing for APOE is not recommended for a number of reasons. First, there is no proven way to prevent or delay Alzheimer disease, and anxiety is common in those who learn they are at an increased risk. Second, the information is of limited use for planning. Most people do not alter lifestyle choices such as career, marriage, or children over the information given its late onset and uncertain emergence. Third, this information could theoretically cause problems when obtaining life or long-term care insurance discrimination. These types of discrimination are not protected by the Genetic Information Non-discrimination Act (GINA) in the US.Despite these drawbacks, those who would like to know this information do seek it out. Due to direct to consumer testing (in states which permit), people can order this test on their own without consulting a physician or genetic counselor. This delivery model is highly controversial because in the absence of genetic counseling, are individuals making informed and thoughtful choices they won’t later regret? Are they aware of the risks and drawbacks to themselves and their relatives? Will anxiety over an APOE 4 result risk extend the negative impact of Alzheimer’s disease beyond the symptomatic years? Despite these concerns, data shows that some people find the information empowering. They use the risk information to seek research opportunities, make healthy lifestyle choices, and/or appreciate life more fully. However, this acclimation usually takes time and develops with the support of knowledgeable clinicians and genetic counselors.APOE testing is here to stay and will likely play a vital role in preventing Alzheimer’s disease once preventive strategies are discovered. Until then, individuals should not enter into testing lightly. It is a tool, and, as with most tools, works best with knowledge and experience.If your health care provider has questions about genetic testing at Quest Diagnostics, they can call 1.866.GENE.INFO (1.866.436.3463) to speak to a genetic counselor.