Genetische Suszeptibiliätstestung für sporadische Alzheimer-Demenz: Analyse medizinethischer Probleme im Spannungsfeld von Autonomie und Verantwortung

Abstract

Alzheimer’s disease (AD) is the most common cause of dementia and a major public health concern. Currently, neither prevention nor treatment exists to cure or stop the fatal disease. Findings suggest that neurodegeneration begins decades before the first symptoms occur. A focus of AD research involves identifying asymptomatic adults at increased risk with the purpose of initiating treatment before the onset of irreversible neurological disease. According to the current state of knowledge AD is a complex disease due to the interaction of genetic and environmental factors. Sporadic late-onset AD is influenced by a variety of genetic factors. The major genetic susceptibility factor is the APOE gene. A variant of this gene, the APOEe4 allele, is associated with a greater susceptibility for developing late-onset AD. Carriers of two APOEe4 alleles are estimated to be up to a 6- to 30-fold increased risk compared to the most common variant of two APOe3 alleles. APOE is an important genetic risk factor but is neither necessary nor sufficient to cause the disease. Due to the limited sensitivity and specificity of APOE testing and the lack of treatment and prevention, APOE testing is not used as a routine test in clinical settings but plays an important role in research settings. Yet, commercial direct-to-consumer (DTC) genetic services offer genetic susceptibility tests for AD over the internet. In this way genetic risk information is available for everybody who is interested and willing to pay for testing via Internet without involving a healthcare professional. In addition to genetic susceptibility testing, other presymptomatic tests such as cerebrospinal fluid and neuroimaging biomarkers are discussed. Regardless of the specific biomarkers that might be used one day, the social and ethical debate will remain the same and the ethical analysis concerning genetic testing for AD can serve as a paradigm: Is there a right to know or maybe even a duty to know about an increased risk for developing AD? The aim of this work is to identify social issues and underlying ethical conflicts concerning genetic susceptibility testing for AD. First, I summarize the findings of empirical studies on socio-psychological implications of genetic susceptibility testing for AD. Second, I undertake a comparative analysis of the existing expert’s guidelines and recommendations concerning APOE testing. Thus I identify public perceptions and values as well as underlying socio-moral and ethical-theoretical reflections in the debate. Through these findings I identify two core ethical aspects of the debate: autonomy and responsibility. Methodically the term ‘responsibility’ serves as an analytic tool to examine social and ethical issues systematically in this context. My context sensitive analysis leads to a normative discussion on how to regulate genetic susceptibility testing for AD with respect to the right of self determination. I point out that there is a right to know in the lack of clinical utility. Thus, the idea of a personal utility in the context of genetic testing needs to be further investigated. One major concern is the availability of personal risk assessment of AD by DTC companies. Since these tests are not followed up by appropriate genetic counseling, their impact on public attitudes should be critically investigated. I critically reject genetic responsibility in the sense of imperative genetic risk assessment as reductionist and misleading concerning Alzheimer’s disease and the complex process of aging. I argue for a broader understanding of responsibility in the context of susceptibility testing for AD that includes social dimensions of responsibility.