A little bit of knowledge: the perils of genetic tests for Alzheimer’s disease

A positive result from predictive genetic testing can give rise to mental health issues, such as depression and suicide. pedro veneroso/Flickr

Genetic mutations are the cause of many incurable diseases and we now have tests to predict the likelihood of people developing inherited diseases. But predictive genetic tests for neurodegenerative diseases have many implications and, for some, such tests are like opening Pandora’s box.

A positive result from predictive genetic testing can impact future health-care and employment options, and give rise to mental health issues, such as depression and suicide. A negative result can bring relief in the knowledge that the disease may have been avoided for current and future generations within a family.

But, in the case of some neurodegenerative diseases, particularly Alzheimer’s disease, the case for predictive testing is not so clear cut.

Genes and neurodegenerative diseases

Neurodegeneration is a term used to describe the progressive loss of function and eventual death of neurons. Some neurodegenerative diseases are associated with autosomal dominant inheritance, which means only one copy of a mutant gene is necessary to cause disease, and each child of an affected parent has a one in two chance of inheriting the mutation.

Causative genetic mutations have now been identified for a number of neurodegenerative diseases. Predictive genetic testing for Huntington’s disease, for instance, has been available for almost 20 years and is considered the gold standard for genetic testing for adult-onset conditions.

But genetically-linked neurodegenerative diseases are rare. Only around 5% of all cases of Alzheimer’s disease, for instance, are classified as early-onset familial versions of the illness. The rarity of hereditary Alzheimer’s has resulted in a medical environment in which the illness is perceived to be one of old age.

This perception is problematic for people in their 30s, 40s and 50s seeking an accurate diagnosis when they begin to show early signs of Alzheimer’s.

Estimates suggest younger onset dementia (dementia occurring in people under the age of 65) currently affects 10,000 people in Australia and about 250,000 people in the United States. Such people, with younger onset dementia, face a unique set of issues. They often have reduced access to support services, for instance, and care providers. Traditionally, patients with the early onset familial form of Alzheimer’s have even been deemed ineligible for clinical trials on the basis of age.

The dangers of testing

Alzheimer’s is a neurodegenerative disease that destroys the learning and memory centres of the brain. It also provides a good case study for the complex issues surrounding predictive genetic testing.

Currently, there are three known genes (APP, PSEN1 and PSEN2) associated with autosomal dominant inheritance of Alzheimer’s. A fourth gene, APOE has been identified as a risk or susceptibility factor.

Genetic testing for Alzheimer’s is controversial due to the complex nature of the disease. Genetic counselling and testing guidelines for the disease have recently been published by the American College of Medical Genetics and the National Society of Genetic Counsellors.

The guidelines are similar to those for Huntington’s disease and involve extensive multidisciplinary consultation with the patient and their family. They recommend against the use of direct to consumer tests, testing in children and APOE testing.

For patients, genetic testing may provide a definitive diagnosis and allow for resolution of matters pertaining to care, family and finances. It also allows interested family members to undergo predictive testing.

But the complex genetics of Alzheimer’s are not completely understood; only an estimated 18% of families with a history of early-onset Alzheimer’s carry an unidentified genetic mutation. Whether other genetic mutations and risk factors influence the age of onset for this type of Alzheimer’s, and how, are also unknown.

So some people using genetic testing may receive a negative result simply because they don’t carry a mutation that’s been identified and characterised but they may still have the disease.

What’s more, the lifetime risk for Alzheimer’s is around 10% to 12% and one in four people over the age of 85 have dementia; a negative genetic result won’t preclude an individual from developing Alzheimer’s later in life.

As public awareness of predictive genetic testing increases, it’s vital that concerned families and individuals have access to the best available support and professional networks. This will help them make informed decisions regarding their options. At the same time, we need more investment in research initiatives for greater understanding of the complex nature of neurodegenerative diseases.