Results and Reflections

Results:

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Over the past four and a half months, my computer has been used to help with the grid computing efforts of the BOINC database. BOINC runs many different programs to help with a variety of research. We specifically wanted to help with the Rosetta@Home project which includes the research of HIV, malaria, cancer, and Alzheimer's. My computer was used for many different projects and probably played a role in researching the protein folding for these diseases.

Reflections:

Kush; Overall, I think that grid computing is very efficient way of solving many problems that require computing power.  Over about a four-month span, it was interesting to see how we were able to contribute to the rest of the grid using Eric’s computer.  We were able to help the BOINC database, which is comprised of a number of different programs that work on research in many different fields including malaria, HIV, cancer, and Alzheimer’s disease.  It’s likely that Eric’s computer helped contribute to research involved with protein folding for some of these diseases.  This was a novel experience for me because I had never known about grid computing and its capabilities prior to our class.  I also thought it was cool because this was one of the few times I've done a service project that relied so heavily on technology.  

Raunak: Throughout this program, I have learned a lot. I had known about Alzheimer's disease before but never actually looked much into it. This project was a great way to learn more. However the highlight of this project was the grid computing. The fact that we are able to help further the research of this disease. I thought it was an incredibly insightful and innovative idea to use multiple computers around the world and have them work together towards a common cause. This teamwork is just what the scientific community needs. Another thing that this project made me think about is the implications of having a disease that disables my memory. It made me think about whether or not I would want such to know if I will end up with this disease.  I know I said earlier that I would want to know but, frankly, I'm still not really sure. Knowing has its benefits but it also has it's downsides. Either way, I am fortunate to not have any family history of it so no need to worry about it, for now. I am just glad we were able to help further the research for those people that do and work towards making their lives and their families' lives a better one. 

Brandi: I really enjoyed this service learning project. I had never heard of grid-computing before and I think it is a very productive way of contributing to research without really having to do much. Before doing this project I didn't really know much about Alzheimer's but I was very excited to learn more about it because my grandfather suffered from this disease. I found it very interesting that the degenerative part of Alzheimer's disease has a path in which it travels throughout the brain. Due to us knowing this, I think we are on a good path of hopefully finding a cure someday and hopefully it is sooner than later. 

Eric: Overall, this project was a really interesting way to get involved in scientific research without really having to do much. While having the program downloaded on my computer, I first had to mess with the settings quite a bit so that I could actually use my computer efficiently while still allowing the program to run. After I was able to figure out what settings were necessary, I just checked it every once in a while to see what it was doing. This project taught me a lot about grid computing and Alzheimer's in a way that was unique and interesting.

Case Study on FFI

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

Both Alzheimer’s and Fatal Familial Insomnia are diseases that onset later in life after the person has most likely already had children which involves degeneration of the brain as well as the formation of amyloid plaques. Both of theses disease have stages in which the disease progresses little by little over time and eventually leads to death. Dementia, as well, is an outcome of both diseases. There is also no cure for either disease.

2. What are prions?

A prion is a protein that is associated with brain tissue and is the protein that is mutated in FFI and Alzheimer’s.  The protein being mis-folded causes the mutation and is named an amyloid fold. This protein can not multiply but it can affect the structure of the tissue because it acts like a template that other proteins start to follow and create the abnormal protein. Due to the number of abnormal templates increasing, there is a substantial increase in the amount of abnormal proteins because there are the more conversions that occur from normal to abnormal.

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?

It is hard for natural selection in nature to act on FFI because the mutation does not occur during reproduction, it occurs within cells in the brain during and after the reproductive age of the person. It can although be acted on natural selection within the cells because it is the competition between the cells that can result in the disease to arise. A high entropy system promotes survival while a lower entropy system can not as readily adapt to changes. Alzheimer’s is also an autosomal dominant disease that does not show symptoms until later in life. This later onset of symptoms is what is keeping these two diseases in the population. Unless the person has some type of gene mapping done they will not know they have either of these diseases until at least 50 years old when they could have already passed on the gene to their children without knowing it.

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?

The abnormal protein folding within the cow can actually be passed onto humans if beef they eat is contaminated with the affected central nervous system tissue. Due to Creutzfeldt-Jacob syndrome and Mad Cow disease being homologous diseases, but in different species, this allows researchers to compare and contrast the diseases.  This is an advantage in the research process because this allows the researchers to examine the different effects in the species that may allow them to make discoveries that were not otherwise possible. Protein folding plays a central role in cell biology so it is inevitable that it will lead to malfunctioning of biology process therefore causing a disease. The number of diseases that are now known to incorporate mis-folding are increasing so it is a very important topic in research so that hopefully a cure can be found before it becomes a much more potent problem.

5. This disease was discussed on Medical Mysteries a few years ago: (https://www.youtube.com/watch?v=Co94aQDs3ek)

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?

Eric: Using genetic testing to determine the risks one has for different diseases is a relatively hot topic right now, some would never do it, and some are all for it. However, if it was up to me, and I knew I had a 50/50 chance of being diagnosed with FFI, I would want to get tested to see if I have those genes. I would want this first of all so that I wouldn't pass it on to any children, which would be the most important thing for me. Secondly, if I knew I was going to have this disease, I believe I would try to do what I could to fight the disease before it was too late, even if there was only a slim chance of the treatment working. Finally, I would use my family history to try to determine when it would likely progress so that I could prepare as needed for my family and friends. In order to prevent passing on the disease and try to give myself time to enjoy life before it was too late, I think I would rather be tested than not for this disease

Brandi: I do not think I would not want to get tested to see if I had such a disease. There is a risk of passing it on to my children but it is not a for sure thing. Because there is not a cure I feel as if you are finding out you have a fatal disease and yet there is nothing you can do about it. With this being the case I feel like I would be living my life just waiting to die. I rather not know and be able to go about my life not waiting for a death sentence I know is going to occur. Although it would be relieving to know if I did not have the disease and not have to worry about it, I do not think it would be worth it. There are so many different things in life that can kill you; I believe that everyone should live their life to the fullest every day because you never know what can happen in the next instance.

Raunak: I think I would eventually want to know if I am going to get this disease. Not now, but probably when I am older and have maybe started a family. If I had a family history of the disease, like the two women did in the video, then I would probably want to know sooner. If I knew about it in time, then I might be able to make proper arrangements for my family and loved ones. I would rather be prepared for it than get me by surprise

Kush: Personally, I would want to know if I had a disease such as FFI.  I would chose this because my awareness of my condition would allow me to plan accordingly for my future i.e. buying a life insurance policy, saving for retirement, planning my mortgage payments, etc.  I would also want to know so I can appreciate each day if I knew I were to die in a short period of time.  It would allow me to shift my focus away from a career and more towards my family, friends, and experiences. Although it would be difficult to live with the knowledge that an illness will kill me, I would rather know about it and have a chance to plan my life so it is still personally fulfilling.

6. The OMIM link above, under “Animal Model”, discusses a phenotype in mice that is similar to that of FFI in humans.  Why, from an evolutionary standpoint, might it be informative for scientists or doctors to study conditions in mice when investigating human diseases like FFI?

This discovery is very important because it is not only the prion that is abnormally folded, but it also have the same sleeping altercations which is different from previous diseases that have been mentioned like Alzheimer’s and Mad Cow Disease. Human studies are very hard to get passed because of FDA regulations. Other animal species, such as mice, have easier access to have a study/experiment passed. Also non-human animals have fewer regulations in which have to be implicated within the study so it is usually easier to be able to perform experiments on the mice than it would be to on humans. With this, more progress is likely to be made in the mice that could then lead to an experiment on humans being endorsed that could hopefully lead to a cure.

http://www-personal.umd.umich.edu/~jcthomas/JCTHOMAS/1997%20Case%20Studies/AAkroush.html

Further reading:  http://omim.org/entry/600072

Interview with Dr. George T. Grossberg, MD

Hello everyone!  
As a member of the EvoSquad, I am proud to present you with an interview we recently conducted with an expert who has in many ways lead the way in research for Alzheimer's Disease.  Dr. Grossberg, a geriatric psychiatrist from Saint Louis University School of Medicine, was generous enough to set aside some time out of his extremely busy schedule so we could share some of his valuable insight on Alzheimer's Disease.  I'd like to thank Dr. Grossberg for volunteering his time for our interview. Enjoy!

About Dr. Grossberg

Taken from: http://neuroandpsych.slu.edu/index.php?page=george-t-grossberg-m-d 

     

     Dr. Grossberg’s professional expertise is devoted to geriatric psychiatry. In 1979 he started the first Geriatric Psychiatry program in Missouri, and in 1985, the first Alzheimer’s Disease Community Brain Bank. He is a former president of the American Association of Geriatric Psychiatry and Past President of the International Psychogeriatric Association (IPA).  He has been a leader in developing mental health programs and in treatment and research in geriatrics. He is a recipient of the Missouri Adult Day Care Association Outstanding Physician Award for supporting programs that allow seniors to continue living independently or at home with their families and the Fleishman-Hillard Award for career contributions to geriatrics.

     Dr. Grossberg has edited 8 textbooks and contributed over 400 articles, chapters, and abstracts to the geriatric literature. In 2007 he published the Essential Herb-Drug-Vitamin Interaction Guide.  He currently serves as medical editor of CNS Senior Care; Section Editor, Geriatric Psychiatry, of Current Psychiatry; and is on the editorial boards of Demencia Hoy, the International Journal of Alzheimer’s Disease, and the Journal of the American Medical Directors Association.  He is a consultant to the pharmaceutical industry in developing protocols for central nervous system disorders in the elderly and is involved in a variety of basic as well as clinical research projects in the area of dementing disorders, with a focus on behavioral disturbances in dementia.

     Dr. Grossberg has served as a consultant on nursing homes to the US Department of Justice Civil Rights Division, chaired the development of Clinical Practice Guidelines for the Treatment of Depression in the Nursing Home for the American Medical Directors Association, and developed educational guidelines on Alzheimer’s disease for the American Academy of Family Practice.

Interview

What is your field of specialty?

Geriatric Psychiatry is one of the newer specialties of American medicine that involves first getting an MD at a medical college, a residency for adult psychiatry for four years, and then doing a fellowship in geriatrics, specifically geriatric psychiatry for at least one year up to two years.  Geriatric Psychiatrists are board certified by the American board of Psychology and Neurology and receive a special certification for geriatric psychiatry from the same board.

What made you choose this field?

The uniqueness of the field, which is a combination of psychiatry, geriatric medicine, and neurology.  What attracted me was this combination because I like being able to learn about the brain-related issues that my patients have, whether they are neurologic or psychiatric, or both.  In addition, I am working with elderly patients that often have co-morbid medical problems and are on multiple medications that contribute or exacerbate neuropsychiatric symptoms.  I find this combination/array fascinating.

How would you define Alzheimer’s Disease in a short sentence? 

Alzheimer’s Disease affects elder individuals over the age of 65 causing forgetfulness, confusion, and progressive decline in cognitive function.  Unfortunately, at the present time, it is incurable.

What is Dementia and how does is relate to Alzheimer’s?

Alzheimer’s Disease is the most common cause of dementia (also known as senility).  Dementia is a general term for the loss of cognitive function associated with old age but can encompass a number of diseases including Alzheimer’s and Parkinson’s disease.

Although the exact cause for Alzheimer’s is still unknown, there are several hypotheses as to what may cause the disease. Could you briefly elaborate on a few of these?

Although we don’t have a cure for Alzheimer’s Disease, I think we have a better understanding of how brain cells die because of the disease.  We have more knowledge of how to potentially delay the onset of the disease and decease the risk of being affected by it.  It seems that Alzheimer’s is caused by the accumulation of a protein called beta-amyloid in the brain which form extracellular plaques.  There are also intracellular tangles which contribute the death of  neural cells, producing the symptoms of Alzheimer’s disease.

How is Alzheimer’s disease diagnosed?

It is a clinical diagnosis based on detailed patient history often from a reliable source other than the patient themselves, such as a family member or close friend.  The patient’s physical and neurological conditions are examined as well, and if there are any progressive changes in memory or cognitive function, further testing involving neurological imaging in conducted to rule out other possibilities.  Ultimately, the combination of results of these diagnostics and the doctor’s knowledge is used to diagnose the disease.

What roles do genetics and lifestyle choices play in increasing or decreasing our risk of Alzheimer’s Disease?

Although genetic risk is unavoidable and plays a significant role in causing the disease, levels of physical, social, and spiritual activity also can have an affect on a person’s risk to the condition.  In addition, lifestyle choices including the food you eat play a role in changing your risks as well.  For example, a Mediterranean diet consisting of high omega-3 fats and low levels of red meat combined with moderate amounts of alcohol can decrease one’s risk to Alzheimer’s.

Currently, what sort of treatment do we use for those affected by Alzheimer’s disease?

There are currently two classes of FDA approved medicines for Alzheimer’s Disease: cholinesterase inhibitors, which have three common medications and NMDA receptor antagonists, which only has one medication, memantine (known as Nemenda).  We are currently using medications such as Aricept, Exelon, and Razadyne (cholinesterase inhibitors) with NMDA receptor antagonists (known as combination therapy) to slow the rate of progression of the disease over time.

What else can people do to reduce their risk for Alzheimer’s?

In addition to the lifestyle modifications I previously mentioned such as changing one's diet, studies indicate that higher levels of cardiovascular fitness are associated with lower risks for Alzheimer’s disease. Maintaining cardiovascular health is another lifestyle modification that can help people reduce their risk to Alzheimer’s even if they have genetic predispositions towards the disease.

How do you think evolution relates to the field of medicine in general and specifically geriatric psychiatry? Why do you think it is important for students to learn and understand the theory of evolution?

Well first of all, I believe that all doctors should believe the theory of evolution because it shows that they are impartial and believe in the scientific process.  It is very similar to a person understanding their cultural/ancestral roots.  When I apply this basic concept of understanding one’s roots to treating patients, I try to understand the “roots” of the patient and where they are coming from.  Understanding the theory of evolution also helps one adapt a mindset that allows us to understand changes in a patient’s interpersonal relationships and find what stressors or environmental factors may affect them.

What do you think about grid computing projects? What kind of role do you think they will play in advancing treatments for Alzheimer’s disease?

I believe that grid computing can play a significant role in Alzheimer’s research, particularly in epidemiological studies for the disease.  I also think that it can contribute by looking at large populations to examine their risk factors and protective factors relative to the development of Alzheimer’s.  I think it is very exciting.

Reflecting on my Experience 

1. Describe your feelings about or response to the interview.

I was excited and interested. I was mainly excited to speak to Dr. Grossberg about Alzheimer's because I wanted to learn more about the disease and how it pertains to those working in the medical field.  Because it is still not completely understood, Alzheimer's disease is very interesting to me.  I am amazed at how far we have come in the recent years with the help of new imaging technology.

2. What changes occurred as a result of your interview? 

As a result of my interview, I have become much more aware of dementia and conditions that are related to it, such as Alzheimer's.  I previously did not know what medications were used to treat Alzheimer's nor did I understand how that medication was administered.  I am also more aware of what I can do to reduce my risk of Alzheimer's disease using minor modifications to my diet and lifestyle. 

3. Did anything about the interview disturb you?

No, nothing about the interview was particularly disturbing.  It was more eye-opening, if anything.

4. Describe the connections found between the interview and your research and classwork.

When connecting our research on our blog to the interview, it was easy to connect Alzheimer's related concepts together.  For example: our research is working with UCLA to determine the primary structure of the protein that accumulates in the brain, beta amyloid.  If we can determine its structure, it opens up the possibility of being able to prevent its formation to prevent Alzheimer's disease.  If this is made possible, new medications and treatment methods might replace and/or modify current medications and methods of treatment.
When connecting Alzheimer's disease to our Evolution class, I found that the two are very similar in the sense that they are both "works-in-progress".  Although we do not know everything about the two subjects, many scientists speculate that Alzheimer's and other neurodegenerative diseases are a result of the evolution of the human brain.  Because our cerebrum is newer than other parts of the brain, it and other more recently evolved parts of our nervous system are more susceptible to such conditions.