Will I Acquire Alzheimer’s Disease or Parkinson’s Disease Based on My Grandfathers’ Experiences?

Recessive and dominant genetic diseases fascinate me, especially given that both of my grandfathers currently suffer from two different diseases that seem to have a genetic component. I often wonder whether I will acquire one or both diseases. The diseases have robbed my one grandfather of his ability to know my mother and her sisters and me and my sisters. The other disease has condemned my grandfather to sitting in a chair all day and sleeping in a hospital bed. Now, both of my grandfathers developed the diseases later in life, which is positive, but the detrimental effects of both diseases on my grandfathers and on my family are apparent and leave me wondering about my health in the future.

     

My grandfather Jimmy and me.

Alzheimer’s Disease

My mother’s father, who we call Jimmy, has Alzheimer’s disease. Jimmy began showing signs or symptoms of Alzheimer’s in 2014 when he was 73 years old and he was officially diagnosed with Alzheimer’s in 2016 at age 75. Alzheimer’s is a devastating disease that destroys memory and thinking skills and prevents people from accomplishing simple tasks. At first, Jimmy became quiet at family gatherings. We thought he needed a hearing aid. Later, Jimmy, who was an attorney, began needing assistance with his cases. At this point, Jimmy met with his primary care physician and eventually with a neurologist. For two years, he was not diagnosed, but then, a cognitive test was performed and during a very sad meeting, the neurologist informed Jimmy and my grandmother that Jimmy had Alzheimer’s. For a few years, Jimmy seemed fine and we learned that he was in the early stage of the disease. He asked the same question a few times and became slightly disoriented. Now, however, Jimmy has progressed to the middle stage of Alzheimer’s. He is no longer sure of who his daughters or his family members are. He also cannot follow simple directions. For example, he does not have the ability to take the garbage out to the garage from the kitchen. He also is unable to unlock the doors in the car and he becomes trapped. In addition, Jimmy cannot put on jackets because his brain now prevents him from deciphering the sleeves.

Chart Depicting the Early, Middle, and Late Stages of Alzheimer’s.

Generally, what happens to the brain of an Alzheimer’s person is that the billions of neurons in the brain, which transmit information by electrical and chemical signals, are disrupted by amyloid plaque, which clumps together between neurons, blocking the communication between these neurons and the signals from flowing. The plaque prevents the neurons from transmitting messages, which ultimately results in loss of function and cell death. In addition, tau proteins clump together inside the neurons, which prevents the neurons from working properly. Ultimately, as the neurons and cells die, the brain shrinks. Usually, this occurs first in the parts of the brain linked to memory, such as in the hippocampus and in the entorhinal cortex. Next, the brain shrinks as the cerebral cortex is damaged, which oversees language. Finally, Alzheimer's damages all of the brain and the brain cannot tell the other body parts how to function. Alzheimer's leads to death not directly from the disease itself, but from other complications due to the disease, such as blood clotting, pneumonia, or other infections. These complications occur because the person has lost the ability to control his or her body.

 

Diagram of a Brain With and Without Alzheimer’s.

While watching Jimmy suffer from Alzheimer’s is very depressing, we as a family try to maintain some normalcy and positivity. I spoke to my grandfather last weekend and he remembered that he played lacrosse in college and that he used a long stick on defense (just like me), but during the same conversation, he became confused and asked my mother the names of her parents. To be honest, Alzheimer’s is a cruel disease and I am curious as to the chances that I may develop it. My mother and I are hoping for a cure one day, which will alleviate the stress of wondering if we will develop the disease.

Determining if I will develop Alzheimer’s through genetic analysis is difficult. For some diseases, it is easier. For example, there is a genetic test to determine if a baby will be positive for sickle cell anemia and there are genetic tests that assist in determining if a woman may develop some forms of breast cancer. With Alzheimer’s, however, there is no definitive test that shows whether I will develop the condition known as late-onset Alzheimer’s, which is what Jimmy has.

There are two forms of Alzheimer’s: early-onset and late-onset Alzheimer’s. Early-onset Alzheimer’s usually occurs before the age of 60. If a person’s parent has early-onset Alzheimer’s, there may be a genetic test for this disease. Some people with early-onset Alzheimer’s have autosomal dominant Alzheimer’s disease (ADAD). This form of Alzheimer's is relatively rare: only about 1% of Alzheimer's patients have ADAD. These individuals have a mutation in at least one allele of their APP, PSEN1, or PSEN2 genes. The disease is autosomal dominant, which means only one of a person’s two alleles for the gene must have the mutation. This means that if one of your parents has a copy of the mutated allele, you have a 50% chance of inheriting that allele. The mutation in these genes causes the production of a bad protein, which builds up plaque in the brain and makes the brain less effective. In a clinical setting, doctors are unable to diagnose early-onset Alzheimer’s more easily than late-onset Alzheimer’s. However, people who test positive for the mutant APP, PSEN1, and PSEN2 alleles have a very strong probability of developing early-onset Alzheimer’s. By having a genetic test, family members may eventually be provided with drugs to help them delay the progression of the disease, especially if researchers can find new drugs to treat the disease. 

Late-onset Alzheimer’s, the disease developed by Jimmy, does not lend itself as much to genetic testing. So far, most of the studies indicate that the genes that make a person more likely to develop late-onset Alzheimer’s are autosomal dominant, not autosomal recessive. A person may develop Alzheimer’s if he or she inherits the allele from only one parent, as opposed to a recessive disease, which requires that you receive the mutated allele from both parents. However, although these genes are autosomal dominant, none of them guarantee that the person will develop the disease. Instead, having the wrong copy of the allele just increases a person’s risk of developing the disease late in life. Also, these genes are not the only causes of late-onset Alzheimer's. It appears that multiple different genes may be involved, but research is still ongoing.

The most common gene associated with late-onset Alzheimer’s is called apolipoprotein E or APOE. There are three alleles of APOE: (1) APOE e2, which is the least common and reduces the risk of Alzheimer’s; (2) APOE e4, which is a little more common and increases the risk of Alzheimer’s; and (3) APOE e3, which is the most common and does not affect the risk of Alzheimer’s. A person acquires one of these alleles from each parent, so he or she will have two of them. If a person has an e4 allele, he or she is more likely to acquire Alzheimer’s, but the person may still acquire the disease even if he or she does not have an e4 allele. So, the e4 allele only increases the risk of developing the disease. In terms of testing for late-onset Alzheimer’s, it does not mean that if a person tests positive for APOE e4, he or she will develop the disease. APOE testing is important for knowing the risk for Alzheimer's disease. Unfortunately, the test does not give a clear answer for whether a person will get the disease and there is no way to prevent the disease. As a result, testing for this gene has been controversial. However, as time goes on, researchers will hopefully either develop a cure or develop more ways to delay or treat Alzheimer's. 

Diagram of the Inheritance Pattern of the Gene APOE e4.

Parkinson’s Disease

My grandfather Rich is my father’s father. He has Parkinson’s disease, which is a disorder that affects the part of a person’s brain that controls movement. It starts with mild symptoms, such as tremors or shaking, and eventually a person’s limbs become rigid or stiff and his or her balance or gait is affected.

 

My grandfather Rich and his grandchildren.

Like Alzheimer’s, Parkinson’s affects the brain. In the brain, there is an area called the substantia nigra, which is located in the basal ganglia. The substantia nigra cells make dopamine, which carries messages around the brain. In a person who has developed Parkinson’s, the cells in the substantia nigra start to die, so a person’s movements are disrupted. Specifically, as the dopamine levels are decreased, the messages are reduced and body movements are unable to function. Unfortunately, Parkinson’s, like Alzheimer’s, has no cure, although there is a medication that assists in the treatment of the disease.

Diagram of a Brain With and Without Parkinson’s.

Rich was diagnosed with Parkinson’s around 2012 when he first started showing symptoms, such as his hands shaking. Over time, Rich lost more and more control of his body. Three years ago, Rich could still walk around and attend my soccer games. Now, however, he can only walk with the help of a walker and he can no longer get up and down stairs. Rich now mainly sits in a chair. He also needs assistance shaving and getting in and out of bed. Rich and my grandmother were very active travelers, visiting China and Australia, and other exotic places. It is sad that they are no longer able to travel and in addition to the physical condition, Rich is depressed because he feels confined to his home and to his chair. Again, I have recently begun to wonder about developing Parkinson’s.

 

Rich in his chair.

The genetic links with Parkinson’s are less clear than with Alzheimer’s. Only 15% of people with Parkinson’s have a family history of the disease. As a result, only for some people can it be assumed that there is a genetic risk. Researchers, though, have identified a number of genes that are linked to an increased risk for developing Parkinson’s. Specifically, a person who has a mutation in the SNCA, PARK2, PARK7, PINK1, and LRRK2 genes may be more at risk. These genes code for different things, but the combination of the genes provides a link to developing Parkinson’s. The genes linked to Parkinson’s can be either autosomal dominant or autosomal recessive. If a person has a mutation in the LRRK2 or SNCA gene, then there is an autosomal dominant pattern. However, if a person develops a mutation in the PARK2, PARK7, or PINK1 gene, then it is autosomal recessive. My grandfather is unsure what mutation he possesses (if any), so it is unclear if I have an increased risk of developing the disease.

Diagram Reflecting the Inheritance Pattern in Parkinson’s.

To know or not to know? That is the question. This famous quote haunts me and my parents. My mother and I decided that we would never be tested even if a definitive test was found for Alzheimer’s. We hope that one day there will be a cure for Alzheimer’s. After discussing the pros and cons, we ultimately determined that we would rather live our lives without worrying about acquiring the disease. On the other hand, my father and I have not decided whether to be tested for Parkinson’s because Rich did not develop any real negative effects until he was 86, so we are less fearful of this disease. Ultimately, the best outcome is developing a cure, so I encourage everyone to think about studying in the field of genetics or on a smaller level, to donate to research for Alzheimer’s or Parkinson’s.

Please visit the links below to donate to Alzheimer’s or Parkinson’s research.

Alzheimer’s: https://www.alz.org/nca/donate.

Parkinson’s: https://www.michaeljfox.org/donate/donate-parkinsons-disease-research.