Alzheimer's disease is one of a growing number of complex diseases influenced by both genetic and environmental factors for which genetic susceptibility testing is possible. Although there are several candidate genes that may influence susceptibility to Alzheimer's disease, the most widely confirmed is the APOE4 allele on chromosome 19, which encodes the apolipoprotein E4 variant.

Background: An introduction to Alzheimer's disease

The presence of an APOE4 allele or alleles may increase lifetime risk of Alzheimer's disease by as much as fifteen times, but is neither necessary nor sufficient to cause the disease. Genetic testing for the variant therefore has highly limited predictive ability and is not generally recommended. However, a paper in the July/August 2004 edition of Genetics in Medicine reports initial results from a clinical trial in the USA that investigated levels of interest in APOE4 testing among adult children of individuals affected by Alzheimer's.

See the APOE gene in the interactive chromosome browser [requires Flash]

The REVEAL study (risk evaluation and education for Alzheimer's disease) is evaluating the impact of risk assessment for Alzheimer's disease using APOE genotyping. A total of 375 participants were recruited via registries of families willing to participate in Alzheimer's disease research or by self-referral on hearing of the project. They received an education session with a genetic counsellor during which the limitations of susceptibility testing for Alzheimer's disease were carefully explained; those who opted to be tested (almost 80 per cent) were randomly assigned to two groups, an intervention and a control group. The intervention group received further genetic counselling based on gender, family history and APOE genotype whereas genotype was not considered in counselling for the control group. Lifetime risk estimates ranged from 13-57 per cent.

Overall uptake of the full testing process was 24 per cent for participants who were initially contacted by researchers and 64 per cent for those who were self-referred. The lower figure is higher than uptake rates previously reported for genetic tests for conditions without effective prevention or treatment options; the higher figure among the self-referred group is not surprising because these individuals had actively sought participation in the trial and hence may reasonably be assumed to have had an interest in genetic susceptibility testing for Alzheimer's disease.

Among participants in the study, key reasons cited for opting for testing included: a wish to contribute to research; the hope that effective treatments would be developed; to inform arrangements for long-term care; and personal affairs and preparation of family members for possible illness. People were more likely to take the test if they were below the age of 60 an/or had a college (university) level education. Most self-referred participants were female.

PHGU comment

The number of patients with late onset Alzheimer's disease is already over half a million in the UK alone; adults with parents affected by Alzheimer's disease therefore represent a large (and increasing) group, many of whom may be interested in options for genetic susceptibility testing.

Although the participants in this study were, as the report notes, not representative of the general US (or UK) population, being predominantly well-educated Caucasians with an active interest in Alzheimer's disease research, even levels of interest in genetic testing for Alzheimer’s much lower than those found in this trial would represent a significant number of people.

If genetic susceptibility testing for the disorder improves in the future (for instance, should more predictive genetic risk factors be identified) or more effective treatment options become available, the demand for testing services could prove to be substantial. Policy and service development would need to take this into account.

Article courtesy of the Public Health Genetics Unit.

Further reading

Roberts JS et al. Who seeks genetic susceptibility testing for Alzheimer's disease? Findings from a multisite, randomized clinical trial. Genet Med 2004 6:197-203. Abstract