Jessica Binder
Neuro 509 paper
(rough draft)
4/11/14
“Autophagy Against Alzheimer’s Disease”
The goal of the proposed research is to test the utility of autophagy against Alzheimer’s disease. Specifically by taking a genetic approach, using a master transcriptional regulator of autophagy, Transcription factor EB (TFEB). For hypothesis-testing purposes, the plan is to genetically accelerate autophagy in microglia, neurons, neuron-microglia, and in animal models of tauopathy. Thus we hypothesize that enhancing autophagy using genetic manipulation will block neuroinflammation, clear intracellular protein-aggregates (MAPT/Aβ), and improve cognitive function in mouse models of neurodegenerative tauopathy.
In 1906, Alois Alzheimer first described Alzheimer's disease (AD) using silver staining techniques to identify amyloid plaques and neurofibrillary tangles. In the brain, neurons connect and communicate at synapses, where tiny bursts of chemicals called neurotransmitters carry information from one cell to another. Alzheimer's disrupts this process, damaging the brain's communication network, and eventually destroys synapses leading to cell death. This phenomenon causes the brain to shrink as gaps develop in the temporal lobe and hippocampus, which are responsible for storing and retrieving new memories. AD is the most common cause of dementia and accounts for 50%-75% of all cases. The two major AD pathologies include amyloid-β peptide (Aβ)-derived extracellular senile plaques and neurofibrillary tangles (NFTs). NFTs consist of intraneuronal aggregates of hyperphosphorylated and misfolded tau that become extraneuronal (“ghost” tangles) when tangle-bearing neurons die. NFTs have a stereotypical spatiotemporal progression that corre...
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...neuroscience research. However, it is not yet clear whether this treatment can be easily applied to humans, besides primary cell culture. Most current experiments are genetically introducing the light-sensitive proteins into selected neurons of mice. This type of targeted neuronal gene therapy would be far more difficult in humans. The other obstacle is that the light activation in the mice required implantation of an optical fiber which directs the light into a specific area of the brain. Performing such an invasive procedure in patients could carry potential risks that would need to be carefully balanced with the risks and benefits. Hopefully, future improvements in gene therapy methods and light stimulation will be able to help overcome these obstacles and pave the way for a whole new class of optogenetics-based therapies in patients with neurological disorders.
The Alzheimer’s Association (2005) defines the disease as “a progressive brain disorder that gradually destroys a person’s memory and ability to learn, reason, make judgments, communicate, and carry out daily activities”. Contrary to popular belief, Alzheimer’s is not the result of normal aging, although it normally occurs more frequently in people who are over the age of 65 (Gruetzner, 1988). Studies performed on the brains of deceased Alzheimer’s patients show several irregularities. The most obvious abnormality is in the signal-transmitting chemicals, where a 40-90% decrease in the enzyme CAT is found. This enzyme lies in the cerebral cortex and hippocampus regions of the brain. When CAT is decreased, it causes cholinergic or acetylcholine-releasing nerve terminals to diminish. These chemicals are important for communication between nerves. Also found during these autopsies were double strands of neurofibullary tangles, senile plaque (decayed neural material), and granulovacular degeneration-all which are associated with mental impairment. Neurofibullary tangles normally do increase with age, but Alzheimer’s patients show a very high density of the tangles. The brain has also been found to contain abnormally high concentrations of aluminum (Weiner, 1987).
Nerve cell death and tissue throughout the brain is the most significant affect over time. Naturally by age twenty-five the brain starts to decrease in size. With Alzheimer’s, the amount decrease is extremely significant. The cortex begins to shrivel up which is the part of the brain required for planning, remembering, and thinking. The most noticeable shrinkage occurs in the hippocampus. The hippocampus is responsible for the formation of new memories, it is also located inside the cortex. Upon further inspection under microscope, tissue samples are observed and synapses and nerve cell count is severely decreased. Tangles, are also found which our twisted strands of another protein due to nerve cells dying and bunching together. Plaques and tangles are prime suspects in the death and tissue loss in the Alzheimer’s brain. Beta-amyloid is a chemical and is sticky which causes it to gradually build up into plaques. This chemical derives from a larger protein found in the nerve cells with fatty membranes. These tangles destroy a vital cell transport system made of proteins.
Alzheimer’s disease or AD is an incurable disorder of the brain that results in loss of normal brain structure and function. In an AD brain, normal brain tissue is slowly replaced by structures called plaques and neurofibrillary tangles. The plaques represent a naturally occurring sticky protein called beta amyloid and in an Alzheimer’s brain, sufferer’s tend to accumulate too much of this protein. Neurofibrillary tangles represent collapsed tau proteins which, in a normal brain along with microtubules, form a skeleton that maintains the shape of the nerve cells. In Alzheimer’s disease, the tau proteins break loose from their normal location and form tangles. Without the support of these molecules, nerve cells collapse and die. As normal brain structure is lost with progression of the disease, brain function also degenerates. Patients afflicted with Alzheimer’s disease display a gradual mental decline. Initially, and most apparently, there is a loss of short-term memory. Eventually, as a patient progresses to later stages of the disease, the brain becomes so damaged that patients can no longer communicate or recognize immediate family or even themselves. They have difficulty walking and standing and frequently fall. In the final stages, they lose bladder and bowel control and have difficulty with swallowing, frequently leaving them malnourished and dehydrated. Eventually, they are forced to remain bedridden and, without the help of life-prolonging measures provided in a hospital, die. However, this level of deterioration is severe and may take as long as twenty years. Because of the disease’s slow progress and its usual later start in a person’s life, a victim of AD will usually die first of natural causes. Under the objectives ...
Clinically, Alzheimer’s disease is characterized by the accumulation of beta-amyloid plaque between living neurons in the brain (Sabbagh, 2008). This results in an excessive calcium influx inside the neurons and the breakdown of a protein called tau. Normally, the rol...
In recent years, teaching religion, or the individual practice of religion in school, has become a very controversial topic. There are many different views on this matter and even more opinions on how it should be handled. There are people on both sides of the spectrum; there are those who believe that it should be taught and allowed in school, and those who believe it should not be taught or practiced in school. If the practice of religion were an option in public schools, students may become more tolerant, as well as knowledgeable, of religions and cultures beyond their own. Secondly, a time interval during the day may be implemented into the school schedule to allow the practice of student’s personal beliefs. Finally, since prayer was eliminated from public school systems, the nation has seen a decrease in education and the increase in crime rate. Even though public schools today are without school prayer, most schools have replaced prayer with a "silent moment of reflection." Prayer should be established into schools, because it generates the exposure to other cultures, allows a calming period for students, and creates well-rounded individuals in society.
Alzheimer’s disease is a complex illness that affects the brain tissue directly and undergoes gradual memory and behavioral changes which makes it difficult to diagnose. It is known to be the most common form of dementia and is irreversible. Over four million older Americans have Alzheimer’s, and that number is expected to triple in the next twenty years as more people live into their eighties and nineties. (Johnson, 1989). There is still no cure for Alzheimer’s but throughout the past few years a lot of progress has been made.
There are three different abnormalities that can make up Alzheimer’s disease. The first abnormality is beta-amyloid peptide cut from APP, a membrane precursor protein (Marieb and Hoehn 2013). Too much beta-amyloid is toxic and causes plaque buildup between neurons that reduces levels of acetylcholine which makes is difficult to retrieve old memories and make new ones (Marieb and Hoehn 2013). Another abnormality of Alzheimer’s disease is the presence of neurofibrillary tangles inside the neuron. These tangles consist of tau, a protein that leaves its stabilizing role and binds to another tau molecule forming a neurofibrillary tangle. (Marieb and Hoehn 2013). Neurofibrillary tangles then kill the neuron. The final abnormality of Alzheimer’s disease is brain shrinkage. The brain shrink...
In the modern age scientists and researchers are constantly discovering new diseases and disorders that affect the human body. With technology improving and new equipment being introduced it enables scientists to gain more knowledge about the disorders than ever before. During the last century a German physician by the name of Alois Alzheimer linked a patient’s memory loss to her brain autopsy which displayed signs of brain shrinkage. His discovery is now known today as Alzheimer’s disease; which is a form of dementia and is a psychological disease that causes the brain to deteriorate. In today’s day and age, there are still many unanswered questions about Alzheimer’s disease (Crider, A., Goethals, G., Kavanough, R., & Solomon, P. 1989). A few known facts are that Alzheimer’s disease is it is most commonly found in elderly humans, with majority of carriers being age 60 or older. It is important to note that Alzheimer’s disease is not an old person’s disease and that it can also be found in adults of younger ages. Furthermore, there are two forms of Alzheimer’s disease. The two forms are called Early-onset which is found in adults ages 30-59 and Late-Onset which is more common and occurs in adults ages 60 and up. Alzheimer’s disease may not be curable, however with the right information it can be easy to conquer (Alzheimer and Dementia Resources).
Alzheimer’s is a terrible disease, the diagnosis of which marks a long and painful journey through neurofibrillary degeneration. Unfortunately, there are so many factors that lead to and expedite the disease that synthesizing a cure is no simple task by any means. Whether the cause of the disease is hyperphosphorylation of tau or beta-amyloid plaques, current medical technology can only delay the symptoms. Hopefully the future of medical research will yield a method for reversing the progression of the neurological degeneration because far too many victims and their friends and family are forced to embark on the long and painful journey of Alzheimer’s.
Alzheimer's disease is the most common form of dementia, and this terminal, progressive brain disorder has no known cause or cure. Its greatest known risk factor is increasing age which is why is it is infamous for developing in the elderly, typically in ages 65 or over, however for the 5%(1) that develop Alzheimer’s in their 40s or 50s it is known as early Alzheimer’s. Because Alzheimer’s worsens over time, those with it tend to struggle with completing daily tasks especially elderly people. Given that there is no cure for Alzheimer’s, the treatments available slow the worsening of dementia symptoms and improve quality of life for those with Alzheimer’s and their caregivers. It is not known what causes Alzheimer's, however, those with Alzheimer's have been found to have abnormal amounts of protein (amyloid plaques) and fibres.(The amyloid plaques and fibres are found in regions of the brain where problem solving and thinking take place e.g The cerebrum.) Due to the unusual amounts of amyloid plaques and fibres, it reduces the effectiveness of healthy neurons and eventually, destroying them.
Alzheimer’s disease is a neurodegenerative disease that attacks and destroys brain nerve cells or neurons eventually killing the cells. It is the most common form of dementia (around 50-60% of all cases of dementia). it affects 1 in 20 people over the age of 65 and 1 in 1000 people under the age of 65. Although it affects more people over the age of 65 it doesn’t mean that age is the cause of the disease. Patients suffering from Alzheimer’s disease suffer from memory loss, thinking difficulty, loss of language skills and changes in behaviour. No one is immune to this disease. Alzheimer’s disease is named after Dr Alois Alzheimer’s. In 1906 he noticed changes in the brain tissue of a woman who died from an unusual mental illness. Her symptoms included loss of memory, language problems and unpredictable behaviour. After her death he examined her brain and found abnormal protein fragments called plagues and tangles. These protein fragments are the two major features of Alzheimer’s disease. The third is the loss of connection between nerve cells and the brain.
Thesis/Preview Statement – Alzheimer’s disease (AD) causes a decline in brain function, it destroys healthy nerve cells. Today, we have discussed Causes, Symptoms, and Diagnosis of AD.
There are over 6,000 discovered genetic disorders that have been passed from generation to generation over the centuries. Most of these disorders do not have a cure and leave many people to suffer. Research has been done with different techniques over the years. In the 1960’s, a new concept called gene therapy was introduced. This technique has proven to be successful as well as unsuccessful in many cases and trials, but as technology is increasing, it gives a new possibility for a cure for genetically inherited diseases such as Alzheimer’s Disease.
Scientists know that Alzheimer disease is characterized by a gradual spread of sticky plaques and clumps of tangled fibers that disrupt the organization of nerve cells in the brain. However , a definite cause, prevention, or cause has not been found.
Alzheimer’s Disease is named after a German doctor, who specializes in the brain and nervous system, named Alois Alzheimer. This Disease forms in the brain. Alzheimer’s is the most common form of Dementia, a general term for memory loss and other intellectual abilities serious enough to enter. The Tau protein ensures the tubes in your brain stay straight allowing molecules to pass through freely. In Alzheimer’s Disease the protein collapses into strands or tangles, making the tubes disintegrate. There is visible differences of brain tissue in the from misfolded proteins called plaques and tangles. Beta-Amyloid clumps block signals and communication between cells in the brain. Researchers agree that Alzheimer’s Disease is m...