This semester, I learned about the background of Alzheimer's, the evolution of the disease, how it relates to Fatal Famial Insomnia, how prions, genetics, and model organisms play a role, and in a more general sense, the importance of grid computing. I have witnessed first hand, with my grandmother, the effects this disease can have on an individual and her family. Through an interview with my mother, her caregiver, I saw that every case of Alzheimer's is different, every story unique. It takes great patience and understanding to care for those with this heartbreaking disease. I am happy to have contributed, even in a small way, to research in this field. Grid computing is a simple, but significant way to help combat diseases. I highly encourage participation in grid computing. I contributed 544.89 units of work to the neugrid. It is a new grid-based research e-Infrastructure that gives neuroscientists support in tackling degenerative brain disorders, including Alzheimer's disease. Dr Frisoni, the head of the Neuroimaging Laboratory in Fatebenefratelli institute , said: 'There is still no biomarker showing whether a drug works or not. Grid-computing can aim at developing markers which are based on images, such as the progressive cortical shrinking during ageing. This will allow people to monitor the progression of the disease and thus the effectiveness of a drug, significantly reducing the number of patients to be followed, on a shorter period of time.' [3]
Friday, May 2, 2014
Sunday, April 6, 2014
Evolution of Alzheimer's and Fatal Famial Insomnia
Fatal familial insomnia is a genetic disorder. It involves the degeneration of the thalamus, the area of the brain responsible for sleep. It involves the development of amyloid plaques, a waxy substance made of proteins associated with polysaccharides. The disease results from a protein mutation. The mutation is the addition of 178 amino acids into the normal protein, turning an asparagine acid into an aspartic acid. This makes it a part of a family of rare neurodegenerative disorders called Prion Disorders. The disease is also autosomal dominant, meaning if the FFI mutated gene is inherited, the individual will have the disease; there are no carriers. Also, both sexes are affected equally.
First, individuals with FFI have a variety of psychiatric problems, such as panic attacks and bizarre phobias. Second, individuals can have hallucinations, panic, agitation, and sweating. Weight loss and premature aging are also symptoms. Finally, suffers reach a stage similar to dementia, where they become mute and experience sudden death. Symptoms do not occur until after puberty.
1. Based
on your research into Alzheimer’s disease and your interview, how are
these two disorders alike?
Both Alzheimer's and FFI involve problems with the brain and therefore have similar symptoms, such as problems with memory, thinking and behavior. Both are also progressive diseases, where symptoms develop slowly and get worse over time, becoming severe enough to interfere with daily tasks. In addition, both diseases prevent parts of the brain cell from working correctly. As damage spreads, cells lose their ability to do their jobs and, eventually die, causing irreversible changes in the brain. Plaques, or protein deposits, develop and inhibit function.
2. What are prions?
A prion is an infectious particle composed of misfolded protein that causes progressive neurodegenerative conditions. It is therefore an abnormal form of a normally harmless protein found in the brain. Unlike other infectious particles, like viruses, it contains no nucleic acid, does not trigger an immune response, and is not destroyed by extreme heat or cold.
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?
Natural selection is the nonrandom and differential reproduction of different genotypes. It is a gradual process by which traits become either more or less common in a population based on relative fitness. It can only have an effect on inherited traits. Because FFI is a is a genetic disorder that can be inherited, it is acted upon by Natural Selection. One of Darwin's postulates is that variation exists among individuals. This variation is due to mutations that occur in the genome of the individual organism, and, therefore, these mutations can be passed to offspring. Because the disease is the result of a mutation of a gene, the gene can be passed on, and future generations can be affected. Therefore, the disease is maintained in the population.
Next, people who have a parent or sibling that developed Alzheimer's disease are tree times more likely to develop the disease than those with no family history. There it is believed it has a genetic basis. Scientists have identified two kinds of genes associated with the familial risk factor. First, a gene called ApoE4 is a "risk gene" that increases the likelihood of developing the disease. Second, a "deterministic gene" is more rare, but if inherited, the person will for sure develop Alzheimer's. Because of this genetic basis, the disease can be obviously inherited throughout the generations. Therefore, Natural Selection can act upon it and it is maintained in the population over time.
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?
Most genes
code for proteins. Therefore, a small error or mutation in a gene could lead
to
an incomplete folding of a protein, which affects its function. When studying
proteins,
one must remember that shape determines function. If a protein is
misfolded, the entire
function will be changed. Over time, more and more research has been completed
looking at the mechanisms of protein folding.
Researchers have gained a better
understanding of how the genetic blueprint of
a protein relates to its biological
function. It has also become clear that wrongly folded proteins are
involved in the
development of many diseases, such as Alzheimer's. If excessive quantities of wrongly
folded proteins begin to collect, they will form piles of unneeded material. This is
known as amyloidoses, a group of diseases in which Alzheimer's is the best-known.
These "piles" of densely packed, insoluble protein cannot be broken down by enzymes.
There are approximately 20 different proteins that can build these amyloidose plaques,
each associated with a different disease. Alzheimer's disease and FFI involve the
accumulation of plaques of insoluble b-amyloid in the brain. As previously mentioned,
the misfolding of the protein dramatically alters its properties. In normal protein,
hydrophobic amino acids are folded inward. If the protein misfolds, these hydrophobic
amino acids are exposed and bind to hydrophobic groups on other protein molecules.
This builds the plaques.
Transmissable spongiform encephalopathies (TSEs), which include mad cow disease
(bovine spongiform encephalopathy; BSE) and Creutzfeld Jakob disease (CJD) in
humans, are special forms of amyloidosis. In these diseases, the brain degenerates,
developing holes and becoming sponge like. This is a result of the aforementioned prion
misfolding. The infectious, incorrectly folded form (called PrPsc) is most likely due to a
genetic mutation. If
we can discover what kind of mutation can cause the misfolding,
then we can try to prevent said mutations.
then we can try to prevent said mutations.
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?
This is a difficult question to answer. I would want to know if I had the disease, because I would not want to have children if I did. As much as I want to be a mother, I would not allow myself to pass on the disease. However, a part of me would want to remain in "ignorant bliss" as long as I could. My quality of life would be so diminished if I knew I was going to develop these horrible symptoms after puberty. This is a question I cannot answer without being in the situation.
6. The OMIM link above [4], 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?
In the study of diseases, it is necessary to use model organisms. The disease needs to be characterized to save lives, and we cannot risk human lives with clinical studies. For example, mice are considered model organisms because they are a non-human species that can be used to understand biological phenomena. They are good examples because they are more prolific and inheritance through generations can be easily tracked. They also have a shorter generation time than humans. Mice also have a similar genome to humans, with orthologous genes, so they are good examples and comparable to humans. Therefore, we can study how gene manipulation in mice will affect humans in a much easier and more ethical way.
[3] http://www-personal.umd.umich.edu/~jcthomas/JCTHOMAS/1997%20Case%20Studies/AAkroush.html
[4] http://omim.org/entry/600072
Monday, March 3, 2014
Interview with a Caregiver
In the later years of her life, my grandmother developed Dementia. Alzeheimer's Association defines Dementia as "decline in mental ability severe enough to interfere with daily life." It is not a specific disease but an overall term that describes a wide range of symptoms associated with a decline in memory and other thinking skills. Alzheimer's disease accounts for 60 to 80 percent of cases.
There was not a specific moment in time when my parents realized my grandmother, Aleen, had Dementia. As time passed, my family just became more and more aware that my grandmother's mental health was declining. As she got older, my grandma became very confused and could not complete day to day tasks on her own. My mother, Janet, had to generously cook, clean, dress, and care for my grandmother. For my mother, she first noticed that Aleen would tell the same stories over and over again, thinking we had never heard them. I remember on my tenth birthday my grandmother gave me a swimsuit meant for a toddler. It was little situations such as those that marked the decline in my grandmother's mental ability.
When my mom first took Aleen to the doctor, my grandmother refused to believe anything was wrong. Later, when she was diagnosed with Alzheimer's, she still maintained that the doctor was incorrect. The adults in my family came together and thought of the best way to handle the situation in support of my grandmother. The first step was telling her she could no longer drive. Then, as she become more and more confused, she had to move from her home to an assisted living facility. My mother said the most difficult part of caring for my grandmother was she her hurt. My grandmother hated getting confused. She never believed anything was wrong with her, even at the end. She would get angry with my mother for trying to help her, she was insistent that she could do everything on her own. My mother had to help her under the radar, without her knowing. Over time, my grandmother's short term memory was next to non-existent. She maintained her long term memory, and never lost sight of who she was nor her family. However, whenever I would visit her, I remember how easily confused she would get. She might forget what she ordered for lunch, or get lost in the grocery store, but she never failed to make me smile, laugh, and tell me she loved me. She was always sharp as a tack, and could teach me so much about life and being a strong woman.
In regards to being a caregiver, my mother said "You just do the best you can. I was still a mother, wife, and employee and had my own life to attend too. You have to remember to take care of yourself when you are also caring for someone else. I was no expert on the disease, I simply loved my mother in law and wanted to help her in any way I can."
My mother also more recently cared for a friend's wife, who was in the late stages of Alzheimer's. She would sit all day with Karen, watching over her, taking walks with her, feeding, bathing, and dressing her. Karen has a more advanced form of Alzheimer's than my grandmother did. Unlike my grandmother, her long term memory was greatly affected. Despite my mother sitting with her all day for weeks, when my mother would return the next week, she would not remember who she was. Karen eventually had to be put in a care facility. My mother misses her gentle demeanor, kind smile, and funny stories.
Every case of Alzheimer's is different, every story unique. One of the things my grandmother taught me, and my mother exemplifies everyday is "Treat others as you would like to be treated." Families face great challenges when dealing with Alzheimer's disease and communication between the involved generations can be one of the biggest struggles. In the words of my mother, "Respect, love, and sacrifice will get you through."
Prayers and best wishes to anyone dealing with this disease, the inflicted and family members alike. If you would like to participate in the grid follow this link: http://www.neugrid.eu/pagine/home.php.
If you would like to learn more about treatment options, the disease, or support please visit: http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp.
There was not a specific moment in time when my parents realized my grandmother, Aleen, had Dementia. As time passed, my family just became more and more aware that my grandmother's mental health was declining. As she got older, my grandma became very confused and could not complete day to day tasks on her own. My mother, Janet, had to generously cook, clean, dress, and care for my grandmother. For my mother, she first noticed that Aleen would tell the same stories over and over again, thinking we had never heard them. I remember on my tenth birthday my grandmother gave me a swimsuit meant for a toddler. It was little situations such as those that marked the decline in my grandmother's mental ability.
When my mom first took Aleen to the doctor, my grandmother refused to believe anything was wrong. Later, when she was diagnosed with Alzheimer's, she still maintained that the doctor was incorrect. The adults in my family came together and thought of the best way to handle the situation in support of my grandmother. The first step was telling her she could no longer drive. Then, as she become more and more confused, she had to move from her home to an assisted living facility. My mother said the most difficult part of caring for my grandmother was she her hurt. My grandmother hated getting confused. She never believed anything was wrong with her, even at the end. She would get angry with my mother for trying to help her, she was insistent that she could do everything on her own. My mother had to help her under the radar, without her knowing. Over time, my grandmother's short term memory was next to non-existent. She maintained her long term memory, and never lost sight of who she was nor her family. However, whenever I would visit her, I remember how easily confused she would get. She might forget what she ordered for lunch, or get lost in the grocery store, but she never failed to make me smile, laugh, and tell me she loved me. She was always sharp as a tack, and could teach me so much about life and being a strong woman.
In regards to being a caregiver, my mother said "You just do the best you can. I was still a mother, wife, and employee and had my own life to attend too. You have to remember to take care of yourself when you are also caring for someone else. I was no expert on the disease, I simply loved my mother in law and wanted to help her in any way I can."
My mother also more recently cared for a friend's wife, who was in the late stages of Alzheimer's. She would sit all day with Karen, watching over her, taking walks with her, feeding, bathing, and dressing her. Karen has a more advanced form of Alzheimer's than my grandmother did. Unlike my grandmother, her long term memory was greatly affected. Despite my mother sitting with her all day for weeks, when my mother would return the next week, she would not remember who she was. Karen eventually had to be put in a care facility. My mother misses her gentle demeanor, kind smile, and funny stories.
Every case of Alzheimer's is different, every story unique. One of the things my grandmother taught me, and my mother exemplifies everyday is "Treat others as you would like to be treated." Families face great challenges when dealing with Alzheimer's disease and communication between the involved generations can be one of the biggest struggles. In the words of my mother, "Respect, love, and sacrifice will get you through."
Prayers and best wishes to anyone dealing with this disease, the inflicted and family members alike. If you would like to participate in the grid follow this link: http://www.neugrid.eu/pagine/home.php.
If you would like to learn more about treatment options, the disease, or support please visit: http://www.alz.org/alzheimers_disease_what_is_alzheimers.asp.
Wednesday, February 5, 2014
Grid Computing
Grid computing is a computer system where interconnected machines take advantage of each other’s resources, such as processing power, memory, and data storage. In a grid, the computers are controlled separately and can perform tasks unrelated to the grid. The grids themselves vary in size. It could be as small as a group of computer workstations in a business, or, as large as many companies networking together. [1] The higher computing provided by grids allows for a common goal, often a complex mathematical or scientific calculation, to be accomplished more efficiently and quickly. Just like a manager of a store distributes work among employees, grid computing shares the workload across multiple computers. This way, there is a bigger pool of resources and less work has to be done by each machine. Grid computing allows one computer to access the collected power of all the networked computers, essentially creating one supercomputer. [2]
For example, neugrid is a new grid-based research e-Infrastructure that gives neuroscientists support in tackling degenerative brain disorders, including Alzheimer's disease. Commenting on the treatment of Alzheimer's disease, Dr Frisoni, the Vice Scientific Director of the San Giovanni di Dio Fatebenefratelli institute in Brescia, Italy, and head of the Neuroimaging Laboratory, said: 'There is still no biomarker showing whether a drug works or not. Grid-computing can aim at developing markers which are based on images, such as the progressive cortical shrinking during ageing. This will allow people to monitor the progression of the disease and thus the effectiveness of a drug, significantly reducing the number of patients to be followed, on a shorter period of time.' [3] In order to participate in the grid, one can download and install secure, free software on a computer, smartphone or tablet by clicking on the following link: http://www.neugrid.eu/pagine/home.php [4]
Alzheimer's is a type of dementia that causes problems with memory, thinking and behavior. The most common early symptom of Alzheimer's is difficulty remembering newly learned information. It is a progressive disease, where dementia symptoms develop slowly and get worse over time, becoming severe enough to interfere with daily tasks. The greatest risk factor is increasing age, and the majority of people with Alzheimer's are 65 and older.
Similar to miniature factories, brain cells receive supplies, generate energy, construct equipment and get rid of waste. They also process and store information and communicate with each other. Scientists believe Alzheimer's disease prevents parts of the brain cell from working correctly. As damage spreads, cells lose their ability to do their jobs and, eventually die, causing irreversible changes in the brain. [5]
For example, neugrid is a new grid-based research e-Infrastructure that gives neuroscientists support in tackling degenerative brain disorders, including Alzheimer's disease. Commenting on the treatment of Alzheimer's disease, Dr Frisoni, the Vice Scientific Director of the San Giovanni di Dio Fatebenefratelli institute in Brescia, Italy, and head of the Neuroimaging Laboratory, said: 'There is still no biomarker showing whether a drug works or not. Grid-computing can aim at developing markers which are based on images, such as the progressive cortical shrinking during ageing. This will allow people to monitor the progression of the disease and thus the effectiveness of a drug, significantly reducing the number of patients to be followed, on a shorter period of time.' [3] In order to participate in the grid, one can download and install secure, free software on a computer, smartphone or tablet by clicking on the following link: http://www.neugrid.eu/pagine/home.php [4]
Alzheimer's is a type of dementia that causes problems with memory, thinking and behavior. The most common early symptom of Alzheimer's is difficulty remembering newly learned information. It is a progressive disease, where dementia symptoms develop slowly and get worse over time, becoming severe enough to interfere with daily tasks. The greatest risk factor is increasing age, and the majority of people with Alzheimer's are 65 and older.
Similar to miniature factories, brain cells receive supplies, generate energy, construct equipment and get rid of waste. They also process and store information and communicate with each other. Scientists believe Alzheimer's disease prevents parts of the brain cell from working correctly. As damage spreads, cells lose their ability to do their jobs and, eventually die, causing irreversible changes in the brain. [5]
 |
| Plaques are deposits of a protein fragment called beta-amyloid that build up in the spaces between nerve cells. Tangles are twisted fibers of another protein called tau that build up inside cells. Plaques and tangles tend to spread through the cortex as Alzheimer's progresses. [5] |
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