Questions on Case Study on FFI

1) Based on your research into Alzheimer’s disease and your interview, how are these two disorders alike?

Alzheimer’s disease (AD) is similar to Fatal Familial Insomnia (FFI) in many ways. For example, both of these debilitating disorders are the result of proteins in the body that have miss-folded. FFI is caused by prions that cause normal prion proteins in the brain to miss-fold just as AD is caused by the random miss-folding of proteins in the brain due to the build up of abnormal metabolites in the brain that trigger the miss-folding of the “amyloid beta” proteins. Another similarity is that the onset of these disorders in humans seems to take place in the later stages of life. A person usually begins to present with the symptoms of FFI between 40 and 60 years of age, with a possibility of symptoms beginning in a person as early as their 30’s. AD also presents in a person later in life as well, with symptoms appearing as early as their late 40’s. Approximately 63% of all people with AD are over the age of 65. These statistics show that both of these disorders present later in life, as opposed to presenting themselves in adolescence, or childhood. Both AD and FFI also are considered to be fatal diseases with no known cure. Because of the rarity of FFI there is little known research on finding a cure for the disease, while there is millions of dollars spent every year on AD research because of its higher prevalence in our society today. Because of this there are treatments for AD, while there are none for FFI. Both of these disorders are life altering and traumatic experiences for one to go through which is why more research is needed in the area of protein miss-folding.

2) What are prions?

The word prion is short for “proteinaceous infectious particle.” They are nonliving, self-replicating particles that are made up of proteins. They are believed to only infect the brain and are held responsible for neurodegenerative diseases such as Alzheimer’s disease (AD) and Fatal Familial Insomnia (FFI). They can arise from a mutation in a gene that code for a protein. They fold into unusual shapes and can cause other proteins to fold into unusual shapes as well which can lead to neurodegenerative diseases. They are believed to be both infectious and also hereditary. The gene that codes for prions can mutate and be passed on to the next generation in a family. However, despite being an infectious particle they do not provoke an immune response which makes it easier for them to cause problems in the brain.


3) FFI is an autosomal dominant disease, meaning that if an individual inherits just one dominant allele from either parent, they will develop the disease. However, this disease does not manifest itself phenotypically until after reproductive age. So can this disorder be acted on by natural selection? What about Alzheimer’s? What is maintaining these disorders in the population?

Yes, this disease can still be acted on by natural selection because it is still prevalent in the individual’s genome. The individual does not need to have the phenotype expressed in order for them to be able to pass on the affected gene. Natural selection acts on genotypes, not the phenotypes of a population. The disorder does not need to be expressed in order for it to be passed from one individual to another. Natural selection does not act on acquired characteristics that one acquires later in life. No, natural selection cannot act on Alzheimer’s disease its self because there is no specific gene that causes AD. Since there is no specific genotype for natural selection to act on then natural selection does not have any effect. FFI is being maintained in the population because it is an autosomal dominant disorder; this means that it only needs one affected gene for the disease to be present. Since it only needs one gene it is more likely that it will continue to be passed on from generation to generation. AD is still maintained in the population because it is caused by random miss-folding of proteins which genetics has no control over. Until we can find a way to inhibit this miss-folding Alzheimer’s will always be present in our population.

4) FFI is caused by a single mutation that, in the presence of methionine at amino acid position 129, changes aspartic acid to asparagine. This same mutation, in the presence of valine at position 129, causes a separate prion-disease called Creutzfeldt-Jacob syndrome. In cattle, the homologous syndrome is Mad Cow disease. How can studying protein folding and mis-folding help in understanding diseases like these?

If we were able to understand protein folding and miss-folding then we would be able to better understand the role of prions in this process. If we were able to understand prions better then maybe we would be able to understand what is causing these mutations in our genome. Having a better understanding of protein folding and miss-folding would essentially allow us to work backwards to eventually learn what is causing these mutations that are ultimately leading to these debilitating diseases. From understanding protein folding better we would possibly be able to reverse its effects on the brain and possibly find a cure to AD and FFI.

5) This disease was discussed last week on Medical Mysteries:
(http://video.google.com/videoplay?docid=760959254431325673&q=fatal+familial+insomnia&total=3&start=0&num=10&so=0&type=search&plindex=0
The two sisters in this story lost their mother to FFI. One sister chose to be tested for the mutation, while the other sister did not. Would each of you want to know whether or not you had a disease such as this, or would you rather remain unaware?

Brad- I would want to be tested for the disease because I feel that I would then have a limited amount of time left. Because of this I would want to know so that I could assure that I would live the way that I want to live in the short amount of time that I may have.

Chelse- I would not want to be tested for a disease like this. Because I don’t want to live my life knowing that it could end soon. If I were to know then I would feel that I have pressure to accomplish what I want to accomplish in life. I would feel that I have a short amount of time to live my life the way that I want.