Having a family history of Alzheimer’s disease might make you concerned about developing it yourself at an older age. In that case, you may want to undergo genetic testing to know about the probability of developing Alzheimer’s.
Multiple researchers have highlighted the link between an increased Alzheimer’s risk and a person’s genetics. Scientific findings show that individuals with first-degree relatives that have had Alzheimer’s are at a greater risk of developing the disease. The risk multiplies further if a person has more than one first-degree relative with Alzheimer’s.
Although scientific advancements, such as genetic testing, can conveniently detect hereditary diseases, the question remains, would it even be helpful to determine an individual’s risk of developing Alzheimer’s via this technique? Before we know the answer to this question, we must know about the genes and genetics of Alzheimer’s disease.
Alzheimer’s Disease and Genetics
Scientists have identified two types of genes, risk genes and deterministic genes, that are associated with late-onset and early-onset Alzheimer’s disease, respectively.
● Risk Genes
Risk genes increase the probability of Alzheimer’s development in an individual but do not guarantee the disease. These genes are associated with the most common form of dementia, the late-onset Alzheimer’s disease. Since its symptoms become apparent after the age of 65, scientists are convinced that it is not solely dependent on genetics.
Instead, other factors, including environment and lifestyle, also contribute to its development.
Researchers have discovered several risk genes. Among them, a genetic variant of the APOE (apolipoprotein E) gene on chromosome 19, APOE ε4, is the strongest indicator of an increased Alzheimer’s risk. Approximately 40-65% of people diagnosed with late-onset Alzheimer’s have this gene.
Besides APOE ε4, there are two more variants of the APOE gene viz. APOE-e2 and APOE-e3. Every individual inherits two copies of APOE genes, one from each biological parent. Inheriting a single copy of this gene increases a person’s risk. Upon inheriting two copies of this variant, the risk is augmented even further, but the disease is not guaranteed. Besides the increased risk, APOE ε4 may potentially be responsible for the onset earlier than usual.
It is important to keep in mind that not everyone with the APOE ε4 gene develops Alzheimer’s. Similarly, a person may develop it without inheriting this variant at all.
● Deterministic Genes
Deterministic genes can directly cause the disease and are responsible for early-onset familial Alzheimer’s disease. In this rare type of Alzheimer’s (which represents only 10% Alzheimer’s patients), symptoms usually appear between the 30s and mid-60s.
Any individual who inherits even one copy of these deterministic genes will develop the disorder due to their autosomal dominant pattern of inheritance. According to genetic scientists, these rare genes are found in only a few hundred extended families around the globe and account for only 1% of total Alzheimer’s cases.
Scientists have identified mutations in three genes located on different chromosomes that are responsible for causing the early-onset type:
- Amyloid precursor protein (APP) on chromosome 21
- Presenilin 1 (PSEN1) on chromosome 14
- Presenilin 2 (PSEN 2) on chromosome 1
These mutations are involved in the production of disease-related abnormal proteins and the degradation of the APP protein. This protein breakdown contributes to the generation of detrimental amyloid plaques, the indicator of Alzheimer’s disease.
Genetic Testing for Alzheimer’s
Although genetic testing can detect both the APOE ε4 gene and rare Alzheimer’s genes, most healthcare professionals do not recommend them for late-onset Alzheimer’s disease. This is because the presence of the APOE ε4 gene does not guarantee the development of Alzheimer’s in an individual, weakening its position as a deciding risk factor. Genetic testing for APOE ε4 is mostly done for research purposes. However, it may be appropriate for diagnosing early-onset Alzheimer’s disease.
Scientists believe that genetic testing may never predict the disease with absolute accuracy because several other factors are also involved in both its development and progression. For instance, an individual may have an increased risk of disease development even in the absence of the APOE ε4 gene due to cardiovascular diseases, environment, or other lifestyle factors.
What to Consider Before Undergoing the Test
A person knowing about their genetic risk factors may be empowering for some while being overwhelming for others. So, before you decide to get tested for Alzheimer’s risk genes or deterministic genes, you must consider the potential emotional consequences associated with the test results.
We recommend that you have a thorough conversation with your healthcare provider or physician before being tested. Furthermore, consider consulting a genetic counselor before and after deciding to take it. The genetic counselor will help you determine which test you should take based on your family history. They will also discuss the prospective emotional impact of results and brief you about the possible consequences of the test, including the effect it might have on your employment, long-term care insurance, and future plans.
