Research into genetic susceptibility to Alzheimer's disease, to be published as "D10S1423 identifies a susceptibility locus for Alzheimer's disease in a prospective, longitudinal, double-blind study of asymptomatic individuals (GS Zubenko, HB Hughes III, and JS Stiffler, Molecular Psychiatry) is addressed by religious scholars concerned about possible public misunderstanding.

"It is important in an area as vague as Alzheimer disease susceptibility genetics that the media not exaggerate the clinical value of new findings. The finding of a locus on chromosome 10 is not new, although this particular study of susceptibility is. Nevertheless, it provides no firm scientific foundation for clinical practice, does not identify the particular culprit gene at this locus, and will require careful further study across various ethnic groups as well as with Caucasians - the only group studied thus far. We are a long, long way from being able to present clearer knowledge of risk based on this chromosome 10 cite.

"The presence of the apolipoprotein (APOE) epsilon 4 allele on chromosome 19 was identified nearly a decade ago as a susceptibility marker for Alzheimer disease. However, it was quickly asserted by no less than five national expert panels that clinical genetic testing for the APOE susceptibility allele was unacceptable because:

"(a) The information provided would be extremely vague and difficult to interpret, so much so that genetic counselors would be hard pressed to provide any valid risk information to at-risk individuals.

"(b) The information provided would be of no medical use to the tested individual, since there are currently no proven preventive interventions available.

"(c) Tested individuals, if carrying the susceptibility gene, would feel unnecessary anxiety over ordinary events such as forgetting where one parked the car, when in fact many people with an e4 allele never get Alzheimer disease, and many people without the susceptibility allele do get the disease.

"(d) Even though the susceptibility information is not predictive for anyone, it would still be legally available to long-term care insurance companies and could easily be used as the basis for refusal to provide coverage.

"(e) Individuals who have a first-degree relative (usually a parent or sibling) with the disease are at somewhat higher than the ordinary 13% lifetime risk; just on the basis of family history, then, we already know that lifetime risk more or less doubles. It is not the case that APOE genotyping would enhance what is already known.

"It is possible that other susceptibility genes will eventually be discovered that allow for a better definition of those at especially high risk than does the APOE genotyping. Over the past decade, several candidate loci on a variety of chromosomes, including chromosome 12, have been announced and touted as the basis for a potential genetic susceptibility test to be coupled with APOE genotyping. However, none of these other purported susceptibility loci have been able to provide further information because they too are so ill-defined and poorly understood epidemiologically.

"Yet eventually, perhaps within a decade, it may become possible to collate a number of genetic susceptibility tests (perhaps as many as a dozen or more will eventually be found) so as to tell someone, whether they have a family history of Alzheimer disease or not, that in fact they really are at very high risk. If so, then perhaps proven therapeutic agents will have been developed to prevent the onset of symptoms or delay their onset. Yet one suspects that if such agents are developed and proven, they will be used widely regardless of susceptibility genotypes, so long as they are not harmful. If these agents do have adverse side effects, then susceptibility genotyping could be useful in sorting out those persons who may well want to take a therapeutic gamble.

"On May 14, 2001, Time Magazine placed on its cover the face of an elderly nun. These nuns have been studied for 15 years by prominent researchers. As the nuns have died, their autopsied brains have been found to all have dense plaques and tangles associated with Alzheimer disease, but remarkably many of them never manifested symptoms. The nun study data indicates that certain personality traits may be preventive of symptoms. For example, optimism and serenity seem to be most relevant, subject to further analysis. This suggests that spiritual and religious practices that enhance optimism and serenity may be useful for ALL of us wanting to avoid the perils of Alzheimer disease, regardless of geneotype. It is classically the role of religion to mitigate the anxiety of life. The belief in providence associated with western faiths allows the individual to accept events and place even difficult times in the hands of an ultimately loving God. Asian religions speak of nonattachment, especially Taoism and Buddhism. Try not to be so attached to one willful course of events, or to material objects, for otherwise serenity is compromised. We may, in the future, come to understand that a spiritual approach to life's inevitable ups and downs over the long haul contributes to healthy aging. If so, new importance will be attached to the old phrases 'Go with the flow' and 'In God we trust.'"

---Stephen G. Post, Ph.D.

"The announcement of each new presymptomatic genetic test has prompted both considerable publicity in the popular media and excitement among those who perceive themselves to be at risk. This latest identification of a new susceptibility locus (D10S1423) for late-onset Alzheimer's disease (AD) promises to produce the same result, especially for first-degree relatives of persons with AD. As another step in the unraveling of the possible etiology of the illness, such research can only be applauded, and we should pursue any therapeutic implications with all diligence.

"The immediate practical benefit of the findings is hard to identify, however, and the way in which the research is likely to be portrayed in the media and interpreted by many people may well lead to some negative outcomes. "Susceptibility" means just that, not certainty, even if the person carries both the APOE E4 and D10S1423 alleles. A test based on this research can at best suggest a heightened risk for AD, a risk of uncertain probability at this time.

"Furthermore, no meaningful treatment for AD exists, and thus--unlike with most cancers, for example--here "early detection" offers no discernible therapeutic benefit. Indeed, it may come with certain costs, not least of which is having to worry longer that every lapse of memory is the beginning of the onset of AD, resulting in an unnecessary or at least premature diminution in quality of life. Expecting to develop AD may cause a person to rush to try any purported "cure," not all of which may be good for one's health. And as for knowing one's fate so that the person can "put his/her affairs in order," even if the test is predictive in a given case, in most cases the progression of AD is slow enough after symptoms appear to allow this to be done.

"Our society is not kind to the elderly as a group, and dementia makes such devaluing worse. Indeed, we have little use in general for those who are considered in any way not to be "whole." Knowing early on that one is likely to manifest AD may well lead not only to a heightened feeling of uselessness on the part of the person but to potential increased discrimination from others, practically speaking in terms of such things as obtaining insurance and various kinds of health care (will a person with high susceptibility be seen as a good candidate for a procedure like an organ transplant?) and more interpersonally by reduction to the status of "person who is going to get Alzheimer's."

"If effective prevention or treatment of AD is developed, it may become possible to argue that early discover of one's susceptibility will be of benefit. At that time it may be appropriate for those at risk to be tested, but that possibility does not justify calling for such an effort now."

--Stephen Sapp

"Research that identifies genetic markers that that show greater susceptibility to late onset (after 60 years old) Alzheimer's disease (AD) is likely to create confusion, and perhaps harm, if not placed within a proper understanding of the science and ethics of susceptibility (predictive) testing. In the past ten years a similar late onset susceptibility testing for the so called "APEO 4" (apolipoprotein E4 gene) has fashioned a unwarranted rush for commercial testing that in turn produced a series of harms to patients and families. These harms ought to be considered before we witness a repeat performance based on today's findings. Today's study provides significant data, namely, asymptomatic family members of persons with late onset Alzheimer's disease who have both the APOE gene and the 234 gene jump from a 10% probability of late onset disorder at age 70 to a greater than 60% probability by age 80 (See Figure 1). Yet the science and the ethics of susceptibility testing should be given serious consideration before creating avoidable harms.

"Consider first the disease and the science. Affecting some 10 million Americans, Alzheimer's begins with insidious loss of memory or other cognitive skills and often culminates in complete dependence requiring assistance with hygiene, nutrition, and supervision of all activities of daily living. Of all persons with AD only 1% have an autosomal dominant gene for early onset Alzheimer's found on chromosome 14 and 21; affected families can be accurately tested for the genes. Surprisingly, a negative test does not mean you won't get AD because there are many other factors that can cause AD. Equally important, unlike tests for early onset Alzheimer's, which are very accurate, tests that indicate susceptibility to late onset AD such as the APOE test are very unclear. A negative test does not mean that you will not get AD--there are other causes of AD not related to APOE. Of all those persons who are diagnosed with AD, the APOE test does not confirm the disease, nor reduce the cost of care.

"Most important, APOE is not a good predictive test. A good test clearly foretells the onset of the disorder. With today's announcement that APOE and 234 genes provide higher probability there is a closer correspondence between the presences of the susceptibility and the risk of the disease--for those people whose have 1) family member already affected with AD and 2) who have both genes. This study does not tell us whether the probability would be as high for a person in the general population if they possess copies of both genes.

"Ethical issues often go unnoticed in the rush to make the tests widely available. Susceptibility testing has greater opportunity for misunderstanding because there is no proof either that with the gene you will get the disease or that without the gene you have dodged the bullet for sure. In the face of uncertain information those tested could get it wrong in deciding major life decisions: schooling, marriage, employment, and insurance. While the risks of knowing might end uncertainty it can also bring a profound sense of loss grief, and mental health problems.

"The religious and theological questions are clearly related to the science and the ethical issues. Knowledge, as uncertain as it may be, can affect one's present and future self-understanding, one's relation to society and the transcendent. This knowledge has a price, not only the potential harms to patients and families, but also to money spent that in justice should have been given to meet health care needs that we can do something about. The Alzheimer's Association, Institute on Aging and Am College of Human Genetics & AM Society for Human Genetics all recommend against using APOE for risk assessment for AD. I think that same reasoning holds true when applied to today's findings."

--Philip J. Boyle

Brief Biographical Sketch: Stephen G. Post, Ph.D., is Professor and Associate Director for Educational Programs, Center for Biomedical Ethics, School of Medicine, Case Western Reserve University. Post has served as Senior Research Scholar in the Becket Institute at St. Hugh's College, Oxford University. He received his Ph.D. in philosophical and religious ethics from the University of Chicago (1983), where he was an elected university fellow. Dr. Post is a member of the Medical and Scientific Advisory Panel of Alzheimer's Disease International. He serves on the National Ethics Advisory Board for the Alzheimer's Association, and was presented with the "special recognition" award by the American Geriatrics Society for service on its Ethics Committee (2001). He was recognized for "distinguished service" by the Association's National Board for educational efforts in bringing ethical issues to Association Chapters and families throughout the United States (1998). His book, The Moral Challenge of Alzheimer Disease: Ethical Issues from Diagnosis to Dying, 2nd edition, fully revised paperback (The Johns Hopkins University Press, 2000) is considered a benchmark in the field.

Provided by Science and Religion News Service, which is committed to providing highly informed, interfaith religious perspectives on breaking news in science. For more information contact srns@science-spirit.org.

---Science and Spirit Magazine

Back to The Science of Mental Health