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Disclaimer — This paper partially fulfills a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering. This paper is a student, not a professional, paper. This paper is based on publicly available information and may not be provide complete analyses of all relevant data. If this paper is used for any purpose other than these authors’ partial fulfillment of a writing requirement for first year (freshman) engineering students at the University of Pittsburgh Swanson School of Engineering, the user does so at his or her own risk.

COMPLEMENTARY α-SHEET PEPTIDES TO POTENTIALLY TREAT ALZHEIMER’S DISEASE

Hannah Liu, hkl11@pitt.edu, Bursic 2:00, Shane McKeon, sdm63@pitt.edu, Bursic 2:00

Abstract— Alzheimer’s Disease (AD) is one of the most common forms of dementia, responsible for 60% to 80%, of cases in the United States and affecting 3-4 million individuals. A major cause of AD is the buildup of plaques in the brain. The plaque begins as an amyloid precursor protein (APP) which is attached to all neurons and is usually cleaved into two fragments by regulatory enzymes to promote neuronal health. However, in a brain with AD, one fragment is cut shorter than usual, causing a portion, the Aβ peptide, to be improperly released and able to interact with other Aβ peptides. These peptides aggregate into complexes called oligomers which continue to fold and adopt an α-sheet structure. These oligomers are toxic to neuronal synapses and can mature into amyloid plaques.  Dr. Gene Hopping at the University of Washington has designed a complementary α- sheet peptide that can bind to the intermediate α-sheet structure of the complexes, inhibiting Aβ maturation and lessening the probability of AD symptoms.

Current treatments rely on early diagnosis, and drug therapy may only yield minor improvements.  Continuing research on α-sheet peptides is imperative as they address an underlying cause of AD as opposed to only symptoms. This innovation will also be described in the context of a clear definition of sustainability. While this new treatment does garner some opposition by raising concerns about surrogate consent, it is still worthwhile to pursue it as a viable option, while finding ways to mitigate concerns.

Key words- Alpha-Sheet Peptide, Alzheimer’s Disease, Amyloid Precursor Protein, Beta-Amyloid Plaque, Surrogate consent

ALZHEIMER’S DISEASE AND THE URGENCY FOR EFFECTIVE TREATMENT

Alzheimer’s Disease (AD) is a type of dementia that most prominently includes symptoms of memory failure; decreased cognitive capability, such as difficulty solving problems or confusion; and consequently irregular behavior and agitation [1]. AD is classified into three stages: mild, moderate and severe [1]. At first, memory loss is mild, but within around ten years an individual will be severely

incapacitated and not be able to respond to their environment, as this disease will always progress until the patient is no longer mentally stable [1].

The most common cause of AD, among another being the growth of neurofibrillary tangles comprised of the protein tau, is the buildup of amyloid plaque in the brain which interferes with neuronal functioning, stemming from mutations in an individual's DNA [1, 2].  AD is also the most common form of dementia, as every 67 seconds someone in the United States develops the disease, while in 2015 an estimated 5.3 million Americans have had or currently have AD [3].  Additionally, with AD being a neurodegenerative disease, its symptoms progressively worsen, emphasizing the need for a new effective treatment, as AD has no cure and a fatal prognosis.  According to the National Institute of aging, the prognosis for AD from diagnosis to death is about three to four years if diagnosed when 80 years of age or older, or up to 10 years if diagnosis was much younger than 80 [4]. 95% of AD cases are people 65 years or older, and as the baby boomer generation is reaching this age, the number of cases is predicted to increase by 40% [3, 5].

Current treatments such as drug therapy aim to lessen the effects of already present symptoms, but the decline cannot be prevented, classifying AD as the sixth leading cause of death in the United States [3].    In this paper, a new and innovative treatment option will be described, specifically an α-sheet peptide that will aim to cure the disease, as opposed to rectifying the symptoms, by directly inhibiting amyloid plaque growth.  An explanation of the abnormal development of amyloid plaque in the brain will be delineated, leading into a description of the α-sheet peptide being explored by Dr. Gene Hopping of the University of Washington. This α-sheet peptide will potentially halt the process of AD.  The innovation’s function, efficacy compared to other forms of treatment, and its ethical implications will be detailed to provide a holistic view of this new option.

BIOLOGICAL CAUSES OF AD

While a few other causes of AD include formation of neurofibrillary tangles and disruption of neural synapses,

University of Pittsburgh Swanson School of Engineering 12016/04/01

Hannah LiuShane McKeon

one of the main causes is the buildup of toxic β-amyloid plaque (Aβ plaque) that can be traced back to a mutation in the gene encoding the amyloid precursor protein (APP) on chromosome 21 [2].  Plaque is the insoluble result of the aggregation of a peptide called β-amyloid (Aβ) which can attach to the synapses of nerve cells, or neurons, in the brain, incurring a decline in memory and cognitive functioning [6]. This complex process will be discussed on a molecular level, as it is this step in the development of AD that will potentially be targeted by the α-sheet peptides.

From APP to Aβ Plaque

The difference between a benign and a malignant track for APP metabolism is very small but can have a large impact.  As seen in Figure 1, APP is a transmembrane protein in all cell membranes of nerve cells, or neurons [6]. Figure 1 displays the APP fragment as a transmembrane protein, meaning one that is partially lodged in the membrane, inhabiting the same environment as γ and α secretases.

FIGURE 1 [6]Illustration of location and orientation of APP in the

neural membrane, and other enzymes, α- and γ- secretases, found in the surrounding area

In a healthy brain, APP is cleaved into two fragments, one larger called sAPP-α and one smaller, by regulatory enzymes, α-secretase and γ-secretase, respectively, as seen in Figure 2 [6].   

FIGURE 2 [6]

Diagram of APP being cleaved into two fragments by α-secretase and γ-secretase. The yellow portion within the

sAPP- α fragment is the Aβ peptide.

sAPP-α contains the region that could possibly become a Aβ peptide, prohibiting the aggregation of Aβ peptides because it encloses this potentially toxic region [6]. Consequently, the development of Aβ plaque does not begin [6].  Both the sAPP-α and the smaller fragment are released to promote neuronal health, such as restoring cell growth of fibroblasts and exhibiting neuroprotective actions against toxic substances [6, 7].  

On the other hand, an individual with AD has mutations on the gene that encodes APP on chromosome 21 [2].  The result of these mutations is proteolytic processing—the breakdown of proteins—of APP by β- and γ- secretases instead of α- and γ- secretases [2]. β-secretase cleaves the APP too short, releasing a fragment called sAPP-β which does not include the Aβ peptide, as seen in Figure 3 [6]. Figure 3 illustrates the first cut made by β secretase, where the APP molecule is cleaved short to produce an sAPP-β molecule, still leaving behind a small part of the APP.

FIGURE 3 [6]Diagram of the improper cleavage of APP, leaving

behind the Aβ peptide. The Aβ peptide is the yellow fragment that is left attached to the membrane.

The γ-secretase then cuts the remaining APP fragment that is still in the neural membrane, which includes the Aβ peptide that can now freely interact with other neurons, as seen in Figure 4 [6]. The toxic Aβ peptide is released into the surrounding environment where other Aβ peptides are being improperly removed as well. This APP fragment that has the Aβ peptide is now collectively referred to as the Aβ peptide.  

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FIGURE 4 [6]Illustration of the final excision made by γ-secretase that

releases the sticky Aβ peptide into the surrounding environment. The yellow fragment is the Aβ peptide.

Aβ is small, soluble, and sticky, facilitating mass Aβ peptide aggregation into insoluble complexes called oligomers [6]. Oligomers continue to grow in size as more Aβ peptides convene, and subsequently mature by folding, adopting a toxic intermediary α-sheet structure [8]. This α-sheet structure stage is unstable and not energetically favorable, and therefore the complexes continue to fold into a final β-sheet structure, characteristic of mature Aβ plaque [8, 9].  

When people usually think of AD they think that the buildup of plaque is the sole cause.  However, the most harm, such as neuronal or synapse damage leading to cognitive decline, is already done by the time the plaque matures [8].  The soluble, intermediary state of oligomers, when they have an α-sheet structure, is responsible for cellular toxicity before continuing to fold into a β sheet structure and, finally, a mature plaque [10].  This toxic intermediary state is being explored by Dr. Gene Hopping of the University of Washington, who has made an innovation that can potentially halt the progression of this intermediate sheet before it causes any harm or continues to develop into an amyloid plaque [8].

FUNCTION AND EFFICACY OF α- SHEET PEPTIDES

Knowing that Aβ plaque has a β-sheet structure that is involved in many degenerative diseases, in 2004 researchers used computer simulations to predict that proteins and peptides actually exhibit a less stable structure called an α-sheet [8]. Using this information, Dr. Gene Hopping of the University of Washington began to design numerous peptides that would have the potential of inhibiting the progression of the development of Aβ plaque.

Purpose of an α-sheet Peptide

An α-sheet structure is adopted by oligomers when they continue to aggregate and fold as a result of improper APP metabolism.  This folding is caused by the carbonyl and amide groups on the individual peptides.  These groups bind via hydrogen bonding to create a polar sheet [10].  This molecular difference of charge continues to build up as more Aβ peptides are released. Individual peptide groups sustain a plane flip to align with the difference in charge to form an intermediate α-sheet [10]. The second image in Figure 5 shows this plane flip, meaning the peptide will flip over in order to gain a more favorable alignment [10].   

FIGURE 5 [10]This diagram illustrates the plane flip that occurs when an α-sheet is formed before the favorable transition to a

more stable β-sheet. The red represents a negative charge and the blue is a positive charge.

After the carbonyl and amide groups align to form an α-sheet, this orientation creates a uniform electrostatic force that creates a larger affinity of the oligomers to each other and increases the addition of further strands [8]. Once the α-sheet is created, transitioning into a β-sheet structure and a mature plaque, or also commonly known as a fibril, is easy as it becomes increasingly favorable to transform into a higher ordered, insoluble amyloid plaque [10].  The fact that the formation of a β-sheet structure and thus the Aβ plaque is so easily facilitated emphasizes the importance of possibly exploring ways in which its development can be prevented and/or inhibited.

Knowing the basic structure of an α-sheet, Dr. Hopping chose to investigate the role that this intermediary state of the peptide plays in the progression of AD.  He began to design a complementary α-sheet peptide that could bind to the harmful backbone structure of the oligomers, the α-sheet structure, and obstruct plaque formation [8].  The project began with the use of a backbone template of an ideal α-sheet design, with the goal of modifying it to fit the α-sheet seen in the simulations [8]. When the designed peptide was added to a solution containing Aβ peptides, it bonded to the harmful α-sheet structure, inhibiting the progression of the α-sheet of the oligomer to a β-sheet, as seen in Figure 6 [11]. The designed peptide attacks the toxic intermediate state, and therefore restrains the formation of plaque [11].  

FIGURE 6 [11]

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This image shows the difference between the development of an amyloid fibril and how the designed

α-sheet inhibits the development.

Possible α -Sheet Peptide Delivery Mechanism

A concern regarding the administration of this treatment is how the peptide will pass the blood-brain barrier (BBB) effectively.  The BBB regulates ion balance and nutrient transport, but most importantly protects the brain from harmful molecules [12].  The blood brain barrier (BBB) plays a crucial role in the communication between the peripheral circulation and the central nervous system [12]. Therefore, the BBB can pose a threat to any therapy of a neurological disease, as it is difficult to surpass the defenses of the brain.  

In AD, the BBB is disrupted as a result of the buildup of Aβ plaque, which can also cause inflammation [12].  Aβ plaque accumulation, inflammation, and the increased permeability of the BBB all simultaneously affect each other [12].  This implies that AD increases the probability that small molecules will be able to enter the brain.  

While disruption of the BBB is harmful in many ways, it can be advantageous as this leaves an opportunity for drugs to successfully enter the brain. For example, this type of delivery of a protein is being explored by Dr. Henry Daniell, a professor in the School of Dental Medicine at the University of Pennsylvania.  He explains that a major challenge to treat neurodegenerative diseases is the BBB and that other invasive approaches like intracerebro-ventricular infusion, convection-enhanced delivery, or microchip systems are inefficient and not patient-friendly [13].  He delivered myelin basic protein (MBP), which has been shown to degrade Aβ plaque, by bioencapsulating it, or covering the active substance with a membrane that will prevent its deformation, and fusing the capsule with a molecule called cholera toxin B (CTB), a small molecule that has the ability to pass through the BBB [13, 14]. To do this, he genetically engineered lettuce plants to express the CTB-MBP compound [13, 14]. Dr. Daniell then orally fed capsules of the freeze-dried lettuce to mice with AD, noticing up to 70% reduction of Aβ plaque levels, showing success in passing the BBB [13, 14].  

Although Dr. Hopping’s α-sheet peptide innovation has not progressed to trials yet, Dr. Daniell’s experiment shows the immense potential and sustainability of the future of Dr. Hopping’s research, in which the α-sheet peptide could be bioencapsulated for administration to a patient.  According to Our Common Future, a report published by the World Commission on Environment and Development (WCED) in 1987, sustainable development can most commonly be defined as “development that meets the needs of the present without compromising the ability of future generations to meet their own needs” [15]. While the development of new treatments does not explicitly concern reducing human’s impact on nature, quality of life and supporting the needs of

the public is a large aspect to consider. The “needs” in this definition that apply most directly to the Dr. Hopping’s research is the support for human and economic, health and vitality [16].

Although Dr. Hopping’s innovation has only been tested in vitro, Dr. Daniell’s research with bioencapsulation is a great example of sustainability and of the path that Dr. Hopping could follow in the future in clinical trials. Dr. Daniell emphasizes that “bioencapsulation of therapeutic proteins by plant cell wall ensures their protection from proteolytic degradation in the stomach and facilitates their delivery to the circulatory system” [13].  This possible drug delivery mechanism is sustainable as the designed protein will not be deformed when traveling in the body and, thus, resources will be used efficiently and not be wasted. Additionally, bioencapsulation using plants is a feasible option, as oral capsules have an extended shelf-life and therefore do not need costly fermentation, like vaccines for example, nor purification, cold storage, transportation, and sterile delivery [13].  This is a great, sustainable alternative to expensive treatments, like drugs and individual care, as AD entails a treatment cost exceeding 600 billion dollars [13]. Sustainability can refer to economic health, and as this potential drug delivery mechanism of the designed α-sheet peptide is easier to produce, maintain and would be less expensive for individuals, this treatment would be more suitable for the masses by being more economically available.

Bioencapsulation is sustainable as well as versatile as it can also be done by other materials, not just with plants, providing many options to consider for delivery of the designed α-sheet peptide. Once α-sheet peptides begin being tested in vivo and in clinical trials, this option of administration through bioencapsulation would prove to be cost-efficient, sustainable and a better, less invasive approach for patients as they could simply take a pill, as opposed to intracerebro-ventricular infusion or microchip systems to pass the BBB as mentioned above.

α-sheet Peptide vs. Similar Complementary Peptides

Starting with the baseline α-sheet structure seen in the computer simulations, Dr. Hopping began designing numerous possible peptides that might bind to the toxic α- sheet formation found in Aβ oligomers. Molecular dynamics (MD) simulation makes this comparison possible, as the system allows researchers to follow the structure and dynamics of molecules in extreme detail [17]. Regarding the designed α-sheet peptides, MD simulations were performed to assess the stability and composition of these peptides through comparison to the MD of the original toxic α-sheet, allowing for an ideal match to be created [8]. Knowing the expected nature of the α-sheet conformation through the MD simulation, the peptides were then stabilized with an amino acid structure that mimicked that of the toxic α-sheet found

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in the body, which would lead to an ideal complementary peptide and more precise bonding between the toxic α-sheet and the designed α-sheet [8].

The designed peptides that looked most similar to the toxic α-sheet peptide were chosen for further testing in two different systems associated with amyloid diseases, one of which was Aβ [8]. Five of the designed peptides were chosen for the experiment. A β-sheet was selected to be a positive control for Aβ, a peptide known as rc to be a negative control, and three α-sheet structures, designed with different alignments amino acids to test for efficacy [8]. Peptides α1 and α3 inhibited 81% and 77% of the plaque formed, respectively, while α1 proved to be stable, inhibiting 87% of plaque formation [8]. After additional stimulation α1 showed 97% inhibition and α3 blocked 96% of the plaque present [8].

Along with halting plaque formation, the α-sheets also needed to be tested for the ability to recognize a toxic Aβ complex when amongst both toxic and nontoxic samples. When the experiment was performed, all three α-sheet peptides bound to the toxic species of Aβ and not the nontoxic species [8]. As a control, the β-sheet peptides were also exposed to the same conditions and they bound to the nontoxic Aβ solutions rather than the toxic samples found in AD, supporting the true efficiency of the α-sheet peptide [8].

Drawing upon the experimental results, all three α-sheet peptide designs bound to Aβ plaque significantly more than the rc and β-sheet controls and these α-sheet peptides were able to recognize toxic Aβ peptides while the controls were unable. These complementary α-sheet peptides are designed to target α-sheet structures in other complexes, not necessarily a specific protein. Being that the designed α-sheet peptides bound so well to the Aβ solution supports the theory that an α-sheet structure is involved in the toxicity of oligomers during Aβ plaque formation [8]. This information serves as the impetus behind Dr. Gene Hopping’s experimental research as he is introducing a new class of amyloid inhibitors, complementary α-sheet peptides, which will target the toxicity in a brain with AD [8].

α-sheet Peptide vs. Current Treatments

While Dr. Hopping’s new innovation provides the possibility of treating AD’s underlying cause, current treatment treatments solely target the expression of patient-specific negative symptoms, which is very limiting for the patient’s prognosis. The first set of potential drugs to reduce symptoms were known as acetylcholinesterase inhibitors (AChE) for their ability to block acetylcholine breakdown enzymes [18]. Acetylcholine is a neurotransmitter, in the synapses of neurons, stimulating the cognitive receptors [18]. The development of AChE medications was based on finding that cognitive pathways in the cerebral cortex and basal forebrain are compromised during AD, resulting in neurological deficiencies [19]. However, it is not proven that acetylcholine has to do with the development of AD, and it

may just be another neurotransmitter impacted by the formation of plaque. The AChE drugs went to clinical trials and did improve functional memory in patients. It was therefore used to delay the cognitive decline associated with AD. However, the drug showed no signs of preventing the eventual progression of the disease [18].

Another leading treatment for AD is the use of NMDA antagonism, designed to block the death of neurons caused by excessive calcium ions [18]. NMDA receptors are known to mediate neurological damage caused by epilepsy, brain trauma, and ischemia [20]. Under normal circumstances, NMDA receptors are blocked by magnesium and are only activated for short periods of time [20]. However, in a brain with AD, the regulation of magnesium is compromised and over activation of the NMDA receptors results in an influx of calcium ions that leads to cell death [20]. The most recent drug to stop the influx is memantine, which binds to the NMDA receptor and blocks calcium ions from entering the neuron, with the goal of preventing neuronal death [21]. By preventing the death of neurons, a patient's cognitive function may be improved, but like AChE drugs, memantine is not attacking AD at its source, but rather makes the disease more bearable. Researchers from the German Institute for Quality and Efficiency in Health Care conducted a study comparing the effects of memantine to a placebo and saw that memantine was able to delay the worsening of symptoms over a period of six months in 1 out of 10 people. However, all patients’ symptoms eventually worsened [21].

Although both of these medications are making strides in the AD community, regarding the definition of sustainability previously discussed, the use of Dr. Hopping’s designed α-sheet peptide better provides for the needs of the public than other treatments. Referring to the fact that sustainability delineates promotion of human health and vitality, this peptide provides for a better quality of life as it will treat the underlying cause of the neurodegenerative disease, AD, as without the treatment symptoms would only continue to worsen until the patient becomes unstable. The new peptide, being developed by Dr. Gene Hopping and his team, is attempting to stop the progression of AD altogether, rather than only lessen the effects of its symptoms which provides a better future for those affected, as the poor prognosis of 3-10 years to live after diagnosis will be potentially eradicated.

ETHICAL IMPLICATIONS

While the prospective of Dr. Hopping innovation is optimistic as it will eradicate the underlying cause of AD, this treatment and research regarding it does entail some ethical issues. Since Dr. Hopping’s innovation is relatively new, with his first findings published in 2014, this technique has not progressed to clinical trials yet.  Therefore, there have not been any documented ethical issues concerning his specific work, but research regarding dementia cases raises

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ethical issues, most importantly and prominently being how surrogate consent is defined, utilized and if it is a sufficient substitution for individual consent given by the person with AD participating in a trial.

Surrogate Consent

Although this topic has been discussed and debated about for decades, there is still no clear policy regarding the involvement of adults with cognitive and decisional impairments in experimental research [22].  When being considered for inclusion in clinical research, those who cannot make their own informed decisions may be allowed to participate through surrogate consent where a family member is usually given the responsibility of making all medical decisions for his/her relative [22].  The main ethical issue, here, is authenticity—where the surrogate must try to decide what the individual with the disease would have chosen if they were capable.  

In the context of AD treatment, this disease is a progressive neurodegenerative disease, rendering an individual unable to make coherent cognitive decisions [22]. In a UK study of participants in an AD drug trial, only 42 of 176 participants were capable of informed consent [22]. Therefore, many individuals with AD who are eligible to participate in trials do not have the decisional capacity to enact their own values or beliefs, allowing a surrogate to fit this role.  However, the patient not being in charge of their own medical procedures raises the question as to whether this treatment is actually in the best interest of the patient, as many treatments involve invasive procedures with unpredictable risks that accompany research procedures including lumbar puncture, drug randomized controlled trial, a vaccine, or gene transfer [22]. Surrogate consent continues to raise questions, but the public’s opinion on dementia research has proven to be positive and promising.

Public Opinion on Dementia Research

As the topic of surrogate consent has been widely debated over the last few decades, Scott Y. H. Kim, Co-Director of the Center for Bioethics and Social Sciences in Medicine at the University of Michigan, designed a survey to be taken by Americans aged 51 and older with a sample of more than 30,000 individuals [23].  Questions concerning one of four randomly assigned surrogate-based research (SBR) were posed to the participants, including a lumbar punctures study, drug randomized control study, vaccine study, and a gene transfer study [23].  Participants answered three questions: “whether our society should allow family surrogate consent, whether one would want to participate in the research, and whether one would allow one’s surrogate some or complete leeway to override stated personal preferences” [23].   The responsibility and complex position a surrogate is placed in to weigh the potential risks and benefits is a critical issue, and therefore, this study was made

to test public opinion in working toward the future of dementia research.

Overall, results from the survey confirmed that the public has a supportive opinion of dementia research and the use of surrogate consent.  The results were that 67.5% to 82.5% of participants support family surrogate consent for SBR, 57.4% to 79.7% of respondents would themselves want to participate in SBR, and 54.8% to 66.8% of these people would give leeway to their surrogates [23].  While there was a large amount of support for the use of surrogate consent and self-participation in research if they were diagnosed with a neurodegenerative disease themselves, the issue of leeway was not uniform.  Leeway is important as it infers that the individual gives full trust to their surrogate in the future as the individual may be increasingly incapacitated at that time, and therefore it is important to note that up to 45% of respondents for the gene transfer scenario would not allow leeway [23].  This survey shows that people trust their family members to make their medical decisions as they lose their decisional capacity.  Also, participants may be more lenient and support surrogate consent if they have exhausted all of their resources and would like to take the risk of participating in clinical trials. By taking the risk, those with AD would be provided with the opportunity to potentially delay or completely halt the progression of their disease. While consent varies on a case to case basis, the public views dementia research positively, leaving a hopeful outlook for the future of AD research.

α-SHEET PEPTIDES AS A VIABLE OPTION FOR AD TREATMENT

While consulting many articles and research-based data and considering the public’s opinions, the future of AD treatment appears optimistic, as Dr. Gene Hopping has provided a feasible option with his new treatment to cure AD. AD is one of the most common forms of dementia, affecting 3-4 million people in the United States alone [1]. As stated previously, AD is caused by an improper removal of the APP molecule from the cell membrane, allowing Aβ peptides to bind together with the eventual formation of plaque that blocks neural synapses. Symptoms, such as memory loss, are produced from the plaque and continue to worsen as the disease progresses, supporting the theory that finding a cure is imperative, especially as the baby-boomer generation approaches the age of onset AD. Previous attempts to help AD patients, such as AChE and NDMA drugs, have only attempted to subside symptoms by supporting neurotransmitters that are negatively affected by AD. Unfortunately, this method of treatment is not sustainable as it does not stop the eventual progression of AD, only makes the patient slightly more comfortable, and costs the US billions of dollars each year. Meanwhile, Dr. Gene Hopping is trying to change the way AD is treated, with an α-sheet peptide that will molecularly stop the

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underlying cause of the disease. By binding to the α-sheet structure of the toxic oligomers, the newly designed α-sheet peptide will consequently block the transition into a β-sheet and therefore prohibit the formation of plaque buildup. Research such as Dr. Hopping’s is groundbreaking as it has the potential to not just subside AD symptoms but improve the quality of life of an individual by extending their prognosis. Additionally, the possible delivery mechanism of this peptide, as illustrated with the example of Dr. Daniell’s research, provides for a more sustainable future for AD treatment, as this peptide will be less expensive than currently available drugs, will be more efficient, will not waste resources, and it will not be invasive.

The importance of continuing the research is not only to help the patient in their day to day lives but to give them a realistic chance at a longer and healthier life. At this time, when a patient receives their prognosis of an average of eight years to live they would immediately turn to treatment and try to slow the development of their disease and consequently, prolong their life expectancy. As stated previously, the patient would turn to the leading medication, AChE and NDMA drugs, which would help with cognitive function and prevent the death of neurons. However, the disease will continue to progress to a point where the patient no longer has control of their own body and cannot complete simple, daily tasks that were easy to them years before, such as making their own decisions. Also, as AD progresses, an individual’s immune system can be compromised, making the patient much more susceptible to a fatal infection. It is for this exact reason that Dr. Gene Hopping’s research needs to be explored, as it has the potential to not only comfort the patient but eradicate AD. Once this new treatment reaches clinical trials, it could have the potential to be more patient-friendly as well as less expensive than other options available. Most importantly, this potential treatment of an α-sheet peptide would prolong an individual’s life expectancy and provide a hopeful prognosis.

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Hannah LiuShane McKeon

[18] C. Belzil. (2007). “Alzheimer’s Dementia.” Lethbridge Undergraduate Research Journal. (online article). https://lurj.org/issues/volume-1-number-2/alzheimers[19] B.B. McGleenon, K.B. Dynan, and A.P. Passmore. (1999 October). “Acetylcholinesterase inhibitors in Alzheimer’s disease.” Br J Clin Pharmacol. (online article). DOI: 10.1046/j.1365-2125.1999.00026.x[20] D. Olivares, V.K. Deshapnde, Y. Shi, D.K. Lahiri, N.H. Greig, J. Rogers, and X. Huang. (2011 Aug.). “N-Methyl D-Aspartate (NMDA) Receptor Antagonists and Memantine Treatment for Alzheimer’s Disease, Vascular Dementia and Parkinson’s Disease.” Current Alzheimer Research. (online article). DOI: 10.2174/156720512801322564[21] (2013 Jul. 18). “Alzheimer's disease: Does memantine help?” Informed Health Online. (online website). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0072540/[22] Scott Y.H. Kim. (2011 May 24). “The ethics of informed consent in Alzheimer disease research.” Nature Reviews Neurology. (online article). DOI: 10.1038/nrneurol.2011.76[23] S.Y.H. Kim et al. (2009 Jan 13). “Surrogate consent for dementia research.” American Academy of Neurology. (online article). DOI: 10.1212/01.wnl.0000339039.18931.a2

ACKNOWLEDGMENTS

We would like to acknowledge Jessie Liu, who took the time and had the patience to help us in proofreading this paper. We would also like to thank Riddhi Gandhi, our co-chair, as well as Dave Gau, our chair, who have been guiding us through this process and proofreading our paper. Lastly, we would like to thank Dr. Budny for this opportunity.

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