Will I Inherit Alzheimer's Disease? The Interaction of the Environment and Genetics

There is a wealth of new research for Alzheimer's disease that seems very promising for the future.

So where does one begin? In this post I am going to review our current understanding of the role of genetics and epigenetics (environmental factors) in developing Alzheimer's disease (AD). Many people are wondering whether they will inherit AD if someone in the family has been afflicted. The answer is clearly not necessarily, as explained below.

Much of the following information is culled from the National Institute of Aging and Medscape

There are two types of Alzheimer's disease - Early-onset and Late-onset (LOAD

Early-onset familial Alzheimer's disease

Early-onset Alzheimer's disease occurs in people age 30 to 60. It is rare, representing less than 5 percent of all people who have Alzheimer's. Some cases of early-onset Alzheimer's have no known cause, but most cases are inherited, a type known as familial Alzheimer's disease (FAD).

Familial Alzheimer's disease is caused by any one of a number of different single-gene mutations on chromosomes 21, 14, and 1. Each of these mutations causes abnormal proteins to be formed.

The single-gene mutations directly responsible for early-onset Alzheimer's disease do not seem to be involved in late-onset Alzheimer's.


LOAD - Late-Onset Alzheimer's Disease

Genetic change can cause a disease directly, but more often acts to increase or decrease a person's risk of developing a disease. This it is called a genetic risk factor. We are now learning that genes can be changed by our environment.

Most cases of Alzheimer disease are the late-onset form, which develops after 60 years of age. The causes of late-onset Alzheimer disease include a combination of genetic, environmental, and lifestyle factors that influence a person's risk for developing Alzheimer disease. The inheritable risk in LOAD is 60-80%, but genetics and environmental factors equally contribute to the onset, progression, and severity of disease.

Researchers have not found a specific gene that causes the late-onset form of the disease. However, one genetic risk factor does appear to increase a person's risk of developing the disease. This increased risk is related to the apolipoprotein E (APOE) gene found on chromosome 19.  APOE comes in several different forms.

• APOE ε2 gene is relatively rare and may provide some protection against the disease. If Alzheimer's disease occurs in a person with this gene, it develops later in life than it would in someone with the APOE ε4 gene

• APOE ε3, the most common gene, is believed to play a neutral role in the disease—neither decreasing or increasing risk.

• APOE ε4 gene is present in about 10 to 15 percent of the population and in about 40 percent of all people with late-onset Alzheimer's. People who develop AD are more likely to have the APOE ε4 gene and tend to develop the disease at an earlier age than those who do not have any APOE ε4 genes.

Although a blood test can identify which APOE genes a person has, it cannot predict who will or will not develop Alzheimer's disease. It is unlikely that genetic testing will ever be able to predict the disease with 100 percent accuracy because too many other factors may influence its development and progression.

One of the biggest limitations of genetic testing is the psychological impact that positive results can have on patients who might have the disease in the future. Surprisingly, the impact of delivering a positive result was studied by the REVEAL trial, which didn’t show any significant long-term psychological impact, depression, or anxiety in patients testing positive for the APOE ε4 gene

The Good News

Epigenetics - The Interaction of Environment and Genetics

Scientists have long thought that genetic and environmental factors interact to influence a person's biological makeup, including the predisposition to different diseases. More recently, they have discovered the biological mechanisms for those interactions. The expression of genes (when particular genes are “switched” on or off) can be affected - positively or negatively - by environmental factors such as stress, exercise, diet, chemicals, or smoking.

Epigenetics is an emerging frontier of science focused on how, and when, particular genes are expressed. Diet and exposure to chemicals in the environment, among other factors throughout all stages of life, can alter a cell's DNA in ways that affect the activity of genes that can make people more or less susceptible to developing a disease later in life. There is emerging evidence that epigenetic mechanisms contribute to Alzheimer's disease. Epigenetic changes, whether protective, benign, or harmful, may help explain why one family member develops the disease and another does not.

Thus it is clear that development of late acting Alzheimer's disease is not written in stone, even with the presence of the APOE ε4 gene. Lifestyle choices can indeed mediate its outcome.