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Genetic Testing: Thinking About An At-Home Test for Alzheimer's Risk Gene? -- What You Need to Know First New York, New York
Persons wishing to learn their genetic risk for Alzheimer's disease -- by way of an at-home genetic test -- should first consider consulting with their doctor and a genetic counselor, according to a commentary authored by AFA's Medical, Scientific & Memory Screening Advisory Board, among other recommendations aimed at physician-scientists, policymakers, and the commercial genetic testing industry. The article was published online by the Journal of Alzheimer's Disease.
"Before pursuing any kind of genetic testing, it is essential that consumers are fully informed and understand the benefits, limitations and other implications of learning one's personal health information," says Charles J. Fuschillo, Jr., President and CEO of the Alzheimer's Foundation of America (AFA). "This includes having insight on how a test result might impact the individual and their family emotionally, particularly in the case of Alzheimer's in the absence of a cure, or an effective treatment."
The number of consumers accessing their genetic information has exploded, since the April 2017 FDA approval of direct-to-consumer testing for genetic disease risks. Among the genetic tests available is one to determine APOE status -- apolipoprotein-E, a "susceptibility" gene for late-onset Alzheimer's disease. And with effective and sustained marketing campaigns by commercial testing entities, the sales of the tests (and presumed use) have already skyrocketed as evidenced by the following reports:  .
"To begin with, people may wrongly confuse genetic risk with genetic certainty -- or a diagnosis; the distinction between risk and causation must be made clear to consumers. APOE genes affect the probability of developing Alzheimer's, but APOE does not by itself cause the disease," cautions J. Wesson Ashford, MD, PhD, Chairman of AFA's scientific advisory board. "It is important to understand that many individuals who have the APOE susceptibility gene never get Alzheimer's. At the same time, not having an APOE susceptibility gene doesn't mean that person will never develop Alzheimer's in their lifetime."
Also, of concern to AFA and its advisory board is that genetic information could be used to negatively impact individual when trying to purchase certain insurance products.
"While the current Genetic Information Nondiscrimination Act (GINA) offers some protections , in a few states -- long-term care insurance and life insurance companies still have the right to ask if an individual knows their genetic status and adjust long-term care insurance premiums accordingly," says Fuschillo. "Therefore, the ways in which personal health information -- including genetic status -- could be used has important implications, posing risks to consumers over which they may have little control."
Consumers should also remain vigilant about the risks of unintended disclosure of genetic testing information through computer hacking or other data security breaches. "As with a person's social security number, a person's genetic information needs to be safeguarded from those seeking the information for exploitative or criminal purposes," says Fuschillo.
On the positive side, research has shown  that individuals who undergo testing and become aware of their own genotype may take pro-active steps to plan for and optimize their future lives, e.g., make lifestyle changes and actually benefit from early detection.
"It's worth noting that those with normal cognition and a genetic predisposition for Alzheimer's may elect to enroll in clinical trials aimed at delaying the onset of Alzheimer's-related symptoms, or preventing it altogether at some point," says Lori Frank, a member of AFA's scientific advisory board.
Some guidance to the lay public is provided by commercial genetic testing firms, but currently there are no industry-wide standards on these consumer guidelines.
Recognizing the level of public interest in genetic testing for late-onset Alzheimer's disease, AFA and its advisory board are recommending that testing companies adopt standardized consumer guidelines and that easy access and/or referrals to appropriate information and resources -- including to qualified genetic counseling professionals -- is provided as part of the testing process.
Some suggest that the physician's office is the only appropriate venue for learning these results, but others disagree. "While physicians certainly could provide appropriate guidance about risk and offer insights into treatment options, the reality is that most clinicians lack the training and report feeling ill equipped to address genetic test results. In our view, given the rapidly growing use of genetic testing, training in interpreting and explaining the genetic test results should be included in the education of health professionals. This training can address when referral to genetic counseling is appropriate," says Frank.
AFA and its advisory board are also calling on researchers to revisit past analysis of Alzheimer's disease genetic disclosure and conduct new research on how such information can influence both negative and positive outcomes, including lifestyle modifications, as well as future planning.
"We recognize the growing importance of genetics in Alzheimer's disease diagnosis, as well as the emergence of personalized medicine, which we hope will one day lead to more effectively targeted individualized therapies. However, we have to do this right and with the best interests of consumers in mind," says Fuschillo. Technical Notes
While APOE is frequently referred to as a susceptibility gene only informing on the risk of developing late-onset Alzheimer's, there are three known "deterministic" (causative) genes for young-onset Alzheimer's, which are quite rare: specific mutations in the amyloid precursor protein (APP), and the presenilin proteins (PSEN 1 and PSEN2) .
These mutations are considered "deterministic" because they cause Alzheimer's disease at a relatively younger age, well before an individual is more likely to die from some another cause.
Nearly all individuals who have one of these mutations in APP or PSEN1 will develop Alzheimer's at a young age. In contrast, mutations in PSEN2 show 95% penetrance, meaning that not everyone with a PSEN2 mutation will get Alzheimer's .
Among the young-onset genetic factors, which include several unknown genes as well, the impairment of memory and other cognitive functions begins before 60 to 65 years of age and accounts for 1 to 5 % of all cases.
By contrast, late-onset Alzheimer's disease, occurs after age 60 to 65 and is the predominant form of Alzheimer's disease . Late-onset Alzheimer's disease is frequently associated with the APOE–epsilon-4 gene. It occurs about 12% of the time in approximately 22% of the Caucasian population, and is found in about 60% of persons with Alzheimer's. The APOE-epsilon-3 gene is the most common form of the gene; individuals with only this gene represent approximately 60% of the U.S. population, but only 35% of the cases. The APOE-epsilon-2 gene occurs about 6% of the time and appears to protect against Alzheimer's disease. Other protective genes against Alzheimer's disease have also been identified.
To date, only health care provider testing is available to identify the rare mutations (APP, PSEN 1 and PSEN2).
Currently, Alzheimer's disease is the fifth leading cause of death in the United States , yet it is the only disease state in the top 10 causes of death for which there is neither a cure nor impactful treatment.
The Alzheimer's Foundation of America is a non-profit organization that unites more than 2,600 member organizations nationwide in the goal of providing optimal care and services to individuals living with dementia, and to their caregivers and families. Its services include a National Toll-Free Helpline (866-232-8484) staffed by licensed social workers, the National Memory Screening Program, educational conferences and materials and "AFA Partners in Care" dementia care training for healthcare professionals. For more information about AFA visit www.alzfdn.org.