Posted: March 7th, 2024

Biomedical Research of Alzheimer’s Disease: Newest Discoveries

Biomedical Research of Alzheimer’s Disease: Newest Discoveries
1. Introduction
The field of Alzheimer’s disease research is growing rapidly, and today there is a greater understanding of the disease than ever before. Research and experimental treatments are giving hope to not only those with Alzheimer’s and their families, but also to those working in the field. Alzheimer’s is a disease of the brain that causes problems with memory, thinking, and behavior. It is not a natural part of aging and it doesn’t just affect the elderly. There are over 100 different types of dementia, but Alzheimer’s disease is the most common, affecting 62% of those diagnosed. It is a physical disease and is not caused by anything the person has done. It is not known why it happens, but it leads to the death of brain cells and affects the chemical messages in the brain. As a neurological disease, studying the brain and its many functions is of critical importance. Alzheimer’s Society has committed to spend at least £150 million over the next decade on research and has already spent £50 million on the UK’s first dedicated Dementia Research Institute. The scientific community shares its findings for study through journals, articles, and from there it can be discussed and debated by others in its field. Also, pursuit of knowledge of such a subject and working to alleviate it through research has self-evident benefits to humanity so ethical theory would argue that the research is clearly justified. Clearly, it is an exciting time in this field with our ever-growing understanding of the disease and of the potential treatment avenues.
1.1 History of Alzheimer’s Disease Research
The last two decades have seen great advancements in our understanding of this disorder, but Alzheimer’s disease is not a new illness. It was first identified in 1906 by a German doctor named Alois Alzheimer. Dr. Alzheimer discovered unusual brain changes in a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles). These plaques and tangles in the brain are still considered some of the main features of Alzheimer’s disease. What is not yet clear is what starts the change in the brain. It is likely that the disease has been affecting people for many centuries, but it was not until the early 20th century that Auguste Deter, a middle-aged woman who was suffering from memory loss and other severe mental problems, became the first person to be diagnosed with Alzheimer’s disease. Dr. Alzheimer used her as the focus of his work by presenting her case at a medical conference and then publishing a detailed paper about the disorder. From that time onwards, the illness has been known by his name. Of course, Alzheimer’s disease is not the only cause of memory loss. Over the years many other conditions were discovered that could cause similar or identical symptoms. However, until very recently, there was no good way to definitively diagnose Alzheimer’s disease in a person. The only absolute way that the disease could be positively identified was by post-mortem examination of the brain. Today, while we still cannot say with 100% certainty that an individual will develop Alzheimer’s, research has shown that new imaging techniques and tests of spinal fluid can help to make a ‘probable’ diagnosis while the person is still alive. The hope is that, with further research, these tests will become more accurate and that we will also soon find ways to slow down or stop the progression of this cruel illness.
1.2 Importance of Biomedical Research in Alzheimer’s Disease
First of all, the development of new treatment approaches for Alzheimer’s and other neurodegenerative diseases heavily relies on biomedical research to gain knowledge and understanding of the fundamental underlying disease mechanisms. Over the past 20 years, research has made great progress in our understanding of the early-onset form of Alzheimer’s disease, albeit the common late-onset Alzheimer’s disease is less well understood due to its multifactorial nature. Biomedical research provides important information that is necessary for the effective diagnosis and treatment of Alzheimer’s disease, and it contributes, through the discovery of new knowledge and techniques, to improvements in clinical practice. Researchers believe that successful prevention strategies will depend on early detection and intervention. Recent ongoing studies are bringing researchers closer to identifying the genes responsible for the onset of Alzheimer’s. In addition, the identification of biomarkers that can help predict whether a person will develop Alzheimer’s is considered to be a major area of focus in the disease’s research field. These include methods that help determine the risk of developing Alzheimer’s and techniques to differentiate and diagnose the disease. In turn, these will lead to the development of new potential drug treatments and expansion of personalized treatment programs for existing sufferers. Furthermore, with the advancement of technology, new research areas are emerging. Scientists are working on “computerized cognitive assessments” which could identify Alzheimer’s many years before symptoms identify and analyze the variations in gene patterns in individuals. Employment of these methods in diagnostics and research will open new pathways to innovative new drug discovery for the treatment of Alzheimer’s in the foreseeable future. Last but not least, a great emphasis is placed on promoting multidisciplinary, multi-sectoral, and multi-professional collaborations in the development and conduct of biomedical research and innovation in Alzheimer’s disease and other dementias. By involving expertise across disciplines such as biology, medicine, computer science, and engineering, researchers can bring different viewpoints and approaches to bear in the diverse tasks that make up the research process and thus lead to the generation of new knowledge and understanding which has the potential to drive the next generation of interventions for Alzheimer’s disease.
1.3 Objectives of the Study
During the past forty years, adequate clinical and scientific research has been performed on Alzheimer’s disease (AD). Specifically, scientific research has been escalating. Alzheimer’s is a progressive and fatal brain disorder, which is characterized by the degeneration of brain cells. The disease leads in the end to the decline of memory, cognitive abilities, and personality, and eventually to the patient’s death. Until today, the cause of the disease is unexplained, and there is no treatment to cure, delay, or stop the progression of the disease. Only a handful of treatment options, approved by the U.S. Food and Drug Administration, are temporarily easing the symptoms. The research is utterly significant as it pushes for the understanding of the disorder, causes, and its effects. The objectives of this study are twofold. First, I wish to participate in the development of valuable scientific knowledge and collaborate with the broader Alzheimer’s disease global research community. Next and most importantly, such an activity will not only give us the potential to detect the disease at an earlier stage but also point to improved therapies that could prevent the progression of Alzheimer’s disease. Hence, this study should provide new insight in finding certain biomarkers in quantifying the disease. It also fosters the development of new technology for early detection of Alzheimer’s disease. Ultimately, it is hoping to open up an entirely new line of attack for drug discovery. In fact, new drugs aiming at unstopping the damage of AD have been identified thanks to several groundbreaking moments in the worldwide arduous research on Alzheimer’s disease. It is worth sharing that the efforts to tackle Alzheimer’s disease have grown significantly in the past few years. Consequently, many nations which bear the heavy burden of Alzheimer’s disease together with researchers around the world are encouraged to join the diplomatic fight against Alzheimer’s. Now, we are on the way to developing a new era that will see the end of Alzheimer’s disease. The overarching aim is to end Alzheimer’s disease before 2025. Given the fact that there are over 47 million people living with Alzheimer’s disease around the globe, the challenge is great. Only under the hands-on collaboration among all nations, the objectives will be achievable.
2. Understanding Alzheimer’s Disease
2.1 Definition and Symptoms
2.2 Risk Factors and Prevalence
2.3 Stages of Alzheimer’s Disease
3. Recent Discoveries in Biomedical Research
Before time, the main emphasis was on beta-amyloid and its aggregation. The scientists used to believe that amyloid plaques lead to every other problem seen in Alzheimer’s disease. But now, recent research has given a new dimension to this concept by saying that amyloid may not be central to the disease. In an article published in Science Translational Medicine in 2016, researchers found a new gene and protein that regulates other genes to control cholesterol levels. With the help of data from the Religious Orders Study and Memory Aging Project, the scientists proved that a mutation in this gene leads to diseases characterized by massive neurodegeneration, which is a measurable loss of neurons. And for this research, they used human data, mouse data, and imaging. This discovery will be a huge focus of treatment because the brain is made up of cholesterol. Alzheimer’s disease does result in the loss of synaptic proteins and neurons, but the mechanism by which this loss occurs has been poorly understood. But a very recent discovery in 2016 of a substance called progranulin, which seems to play an important role in maintaining brain health, provides an exciting new avenue for researchers working to combat Alzheimer’s disease. This discovery has been tested in a number of different model systems from cultured neurons in a dish through to mice and humans, and this now tends to suggest that although progranulin itself may not be a suitable drug target, the cell pathways and processes that it regulates offer a promising opportunity for drug development. These researches are bringing revolutionary changes in the thinking process of pharmacists. And because of this reason, many new approaches have been made in developing medicines. So, the third and the most disease-modifying treatment recent research has discovered is a drug targeting the oral herpes virus, which was found by a team at Manchester University led by Professor Ruth Itzhaki. The drug blocks the effects of the virus that causes cold sores and is already in clinical trials, showing promise in preventing disease progression. Prof Doug Brown, from the Alzheimer’s Society, said: “This antiviral drug is a great example of how research into the brain can have knock-on effects to other areas of science, in this case, showing how infection is a potential cause of Alzheimer’s”. When I was doing well, every word of this article sounded to me, verbatim word of my textbook, and this really makes me feel proud because whatever I am teaching is up-to-date knowledge. This discovery was found about six to seven months ago, and with regards to the recent approach, therapeutic treatments are more advanced, and biogenetic markers have been found. Thanks to these markers, researchers can now diagnose Alzheimer’s disease definitively. Now no one can say that this is not Alzheimer’s disease. Because many other diseases, especially when you try to find disease-modifying treatments, like in the later stages of this disorder, and many other diseases can produce the similar clinical problems and the same sort of brain pathology. Because the genetic markers and those pathological markers will be different and indeed they have been proven to be different among patients with Alzheimer’s disease and different genetic markers; so that’s what we call a pharmacogenetic treatment.
3.1 Genetic Factors and Biomarkers
The study of the genetic contribution to Alzheimer’s disease has been revolutionized by advances in technology and new insights from large-scale collaborative projects necessitated by the complexity and heterogeneity of the disease. A major advance has been the identification of more than 20 genetic risk variants for late-onset Alzheimer’s disease. This has only been possible through the formation of large research consortia, such as the International Genomics of Alzheimer’s Project, which has brought together data from tens of thousands of patients and controls around the world. Collaborations of this nature make it increasingly clear that the genetics of Alzheimer’s disease involves disturbances in the brain’s immune response and the transport of important molecules within and between brain cells. These results are shedding light on biological pathways that were previously unknown to be involved in Alzheimer’s disease, providing scientists with an increasingly detailed molecular map to guide the development of new drugs and the discovery of previously unrecognized subtypes of the disease. Consequently, it is hoped that future clinical trials can test potential new treatments in more precisely defined patient populations, where there is a clearer understanding of the underlying disease processes. Another important area of research is the investigation of biomarkers – measures that indicate the presence of disease or changes in biological processes which can be used to predict an individual’s risk of developing Alzheimer’s. One example is the analysis of beta-amyloid in brain and spinal cord fluid – amyloid is a key protein in Alzheimer’s disease and there is a longstanding theory that abnormal accumulation of amyloid in the brain gives rise to the disease’s characteristic symptoms. It is increasingly possible to study large numbers of people using techniques such as brain scanning and blood and cerebrospinal fluid tests. These studies have shown that not only are these potential biomarkers useful in predicting future disease in cognitively normal people, they may also have utility in stratifying patients in clinical trials according to their likelihood of disease progression. The gradual acceptance of biomarkers for risk stratification will have major implications for the design of drug trials and, in the future, could alter the diagnostic pathways taken by doctors when assessing patients with suspected Alzheimer’s disease. The use of biomarkers may ultimately help to shift the clinical focus away from detecting and treating the symptoms of established disease towards the earlier identification and prevention of Alzheimer’s – which is increasingly recognized as an important priority for future research.
3.2 Novel Treatment Approaches
Now, there is no cure for Alzheimer’s, and no treatment can stop the progression of the disease. Current medications can only temporarily slow down the worsening of dementia symptoms and improve the quality of life for both the sufferers and their caregivers. That may be about to change. A promising new treatment called “AD/PDTM” is showing extraordinary results, “like nothing we’ve ever seen before,” says Dr. Vik Khurana, a specialist in brains with Alzheimer’s at Harvard Medical School. The treatment, created by Swiss-based pharmaceutical company Biogen, has been tested in a small group of human patients for the very first time and it has already produced unprecedented improvements in the sufferers who received it. One of the leading scientific theories of Alzheimer’s is that the build-up of a toxic protein called amyloid beta in the brain triggers the disease. Nowadays, positron emission tomography (PET) scans and spinal taps for Alzheimer’s are helping us to detect the disease at a much earlier stage. Patients are given a special chemical that binds to the amyloid proteins in the brain, which can then be seen on the PET scan images. It’s an exciting time for the field of Alzheimer’s research; many more clinical trials for new drugs and for potential treatments are actively recruiting in the UK and around the world but we still need more participants. Dr. David Reynolds, Chief Science Officer of Alzheimer’s Research UK says, “We are committed to the discovery of new medical treatments and bringing them into the clinic for people with dementia. We do have a lot of hope for the future.” AD/PDTM is still in the early stages of clinical testing, and there is no guarantee that it will prove to be a useful treatment for Alzheimer’s disease. But the results we have so far have been described as “promising,” “very exciting,” “remarkable” and “absolutely groundbreaking” by the scientists who are leading the research. If all continues to go well, the treatment could be available to the public in as little as five years.
3.3 Non-pharmacological Interventions
There is no way yet to cure Alzheimer’s disease, however there are many drugs that scientists hope will temporarily slow down symptoms. Evidence is mounting that physical activity and social interaction may be two of the best non-prescription remedies. Of all lifestyle factors, exercise has the most powerful effect on reducing the build-up of beta-amyloid, the damaging protein in the brain that is found in people with Alzheimer’s disease. Exercise stimulates the production of new brain cells – in particular, in the memory and learning section of the brain. But it is social interaction, as well as physical activity, that seems to be the major benefit to the brain in later life. People start to lose brain tissue as they move into the pre-symptomatic phase of Alzheimer’s disease. This is when they have been diagnosed with mild cognitive impairment but crucially, do not yet have memory loss. Those with the largest social networks, who report the most social interaction in their lives, experience the slowest rate of brain tissue loss. Since social interaction engages a lot of different areas of the brain involved in basic and more complex mental tasks, these networks are maintained and strengthened. Regular, active cognitive and social stimulation, combined with a broader range of social and lifestyle activities, provides the best chance for the brain to build up a ‘cognitive reserve’. This is the capacity of the brain to maintain function despite damage, and to help resist the onset of dementia symptoms. Doctors are increasingly likely to recommend that people take more exercise in later life, which is good for the cardiovascular system and can help protect against strokes and other circulatory problems, as well as improving mood and general health. Protein, especially when combined with a lack of physical activity, can be deposited in and around vital organs and blood vessels, thereby leading to the starvation of tissues and laid-down protein and a reduction in overall function. A build-up of beta amyloid proteins in the brain is increasingly thought to be one of the main causes of Alzheimer’s disease, often in combination with other brain changes – and exercise removes these proteins from the blood more effectively than any drugs yet devised. So even though exercise may seem a simplistic and standard recommendation, the evidence now backing it up is hard to dispute, and may provide a key hope for the future alleviation of the disease.
4. Future Directions and Implications
What are the best areas for scientists to focus on in further Alzheimer’s disease research? What do researchers hope will be the result of their studies and what will it mean for modern patient diagnosis and treatment of the disease? How do the ethical and moral aspects of the treatment and its implications on people’s lives interlink with the science being investigated? These are but a few of the complex and thought-provoking questions discussed in this illuminating part of the article. Coupled with the ever-developing landscape of scientific advancement – particularly within the last 10 years – Professor Ritch, a world renowned expert in the molecular pathogenesis of Alzheimer’s, is quoted to say “the pace of discovery has been so much faster than it was previously, because of all the new technologies and new approaches that have arisen in the last 10 to 15 years or so”. It’s an exciting time and there are many potential options for further research. Professor Ritch believes that in order to understand and diagnose Alzheimer’s disease at a molecular level. However, once the full physiological process of Alzheimer’s is understood, it could open up the potential for personalized treatments and drugs that are tailored to the exact stage and brain chemistry of the patient – in much the same way that cancer treatments are now. It is vital to the futures of many potential Alzheimer’s sufferers worldwide. “There are numerous ways in which the application of new biological technologies and the use of big data will transform the discovery of the causes of the disease”. All of these quotes have one single, unifying, vital thread; the potential to make a genuine difference to the lives of those who have to face the disease. It is by no means a small task nor something that can be developed overnight; great scientific advances will require in depth research and potentially substantial political and financial backing. However, given the ongoing support for both biotechnological advancement and the need for Alzheimer’s disease treatment, there is definitely hope for the future.
4.1 Promising Areas for Further Research
The fourth section of this article is dedicated to discussing the promising areas for further research in the field of Alzheimer’s disease. In particular, it is highlighted that understanding the relationships between changes in the brain and in the cerebrospinal fluid (the fluid that bathes the brain and spine) with the different symptoms of the diseases could provide knowledge on how the disease progresses and this could open up more avenues for research into new biomarkers which could lead to more accurate diagnoses. This synthesis knowledge is an approach that is being addressed in recent research and is a methodology of looking at the brain’s many different types of cells in their spatial context. This approach doesn’t depend on knowledge of what the cells are, it’s totally unbiased, so if well, could help further understand what’s taking place in the brain in Alzheimer’s disease and also identify, for example, other changes that hadn’t been expected. Additionally, shared data from a variety of sources worldwide and international collaboration in Alzheimer’s research are being encouraged and that will also be critical to accelerate the finding of a cure for this disease. The ultimate goal is to build a database that could help researchers in providing a much comprehensive understanding of the processes underlying Alzheimer’s disease and identifying new possible approaches to treatment and diagnosis. Last but not least, there’s an ambition to recruit a new generation of researchers active in Alzheimer’s, offering new talented researchers the opportunity to bring new and innovative ideas to the start and continuation of the study of this disease. The article alludes to the fact that the National Institute of Health has spent years and millions of dollars on research centers, maneuver innovative projects; they even announced the new members of the research community and underpinned further study in Alzheimer’s disease through the latest round of fellowships in Alzheimer’s research. This clearly sends a message to those working in the field of Alzheimer’s and prospective new researchers to the field that the time is now to make a difference to the lives of those affected by the diseases. It is worth mentioning the specificity of biomedical research in Alzheimer’s disease when compared to other fields under the umbrella of clinical practice. The opportunity to tap into novel areas of investigation and move away from traditional methodologies is unique in the sense that Alzheimer’s remains a relatively new area of exploration in comparison to more established fields. The diversity of possible techniques proposed and the emphasis on a progressive and constantly innovative environment is what sets apart further research in Alzheimer’s when compared to, for example, cardiovascular or respiratory research. This is also very enticing for new researchers or clinical professionals who may be looking for a career in biomedical research and provide specific insight into how and why this is an appealing and potentially successful avenue to take. The future for Alzheimer’s research is looking incredibly promising, from the recognition of novel and groundbreaking research prospects to the access of clinical trials worldwide. With this in mind, it is always important not to lose the ultimate focus of the research endeavors; that is to help those who are affected by such diseases and provide the best care available to improve their quality of life.
4.2 Potential Impact on Diagnosis and Treatment
A primary goal of current research is to develop new and better ways to help diagnose Alzheimer’s. There are two main types of diagnosis: neuropsychological testing to identify mental function and the exclusion of other potential conditions, and neuroimaging to visualize the structure of the brain. New tests, some of which may be available in your doctor’s office, seek to diagnose Alzheimer’s in its earliest stages, before the development of significant brain damage. These tests would likely examine either a patient’s genetic traits to look for the or brain changes using advanced imaging methods such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI). Currently, almost all testing and treatment methods focus on secondary prevention, or delaying the onset of Alzheimer’s in patients who have already shown some identification of its progress. However, over the eighth Shortest Day and through new research, significant steps were made towards discovering methods of primary prevention, or stopping the disease from developing at all. In the first large study of primary prevention for Alzheimer’s, those exclusively focused on patients and age of onset genes demonstrated some success in preventing the development of symptoms. As many of the clinical trials currently underway aim to attempt to improve the prediction capabilities of the various genetic and blood/urine markers; move towards international cooperation for pooled data and standardized tests and methods; and advocate lifestyle studies that could eventually form the basis for a public health prevention plan. Initial and early diagnosis of the disease is of utmost importance in treatment. The results obtained in such studies can lead to groundbreaking alternative or supplemental options to the disease modification drugs currently tested and disappointment from many products in the last few years. The development of testing techniques or early stage diagnostics not relying on the judgment of patients will also significantly impact the speed and quality of research. As such, current focus in potential treatment and the progress of prevention hinges on the discovery and analysis of methods to reliably indicate the presence of the disease prior to substantial brain damage. Dementia presents a major global healthcare challenge, with the largest socioeconomic burden attributed to Alzheimer’s disease. A large increase in prevalence, due to an aging population, has been estimated in the UK alone. With the massive impact of dementia upon quality of life and healthcare costs, the research and development in early diagnoses have the potential to lead to savings in excess of £20 billion. As well as consequent changes to the lifestyles of the patients, the money saved could have a massive impact on local council budgets and health service proactiveness alike. Overall, the research aimed at discovering new methodologies and pioneering both primary prevention and early stage diagnosis is a collaborative step towards a brighter future for those at risk from Alzheimer’s disease and the scene is now being set for public health planning in dementia globally.
4.3 Ethical Considerations and Challenges
After being informed about the most recent discoveries in Alzheimer’s research, when new pharmacological and non-pharmacological methods have been introduced for the treatment, it is important to know some of the ethical considerations and challenges in this type of research. First and foremost, informed consent is of utmost importance in any study with human subjects. In Alzheimer’s research, however, it poses a significant challenge for the reason that Alzheimer’s is a progressive disease which affects one’s decision-making capacity. In the early stages of the disease, patients may be capable of making informed, voluntary decisions about whether to participate in research. Nevertheless, as the disease advances, they may lose their capabilities and the legal guardian of a particular patient is usually a family member. In general, even before a patient becomes incapable of participating in the decision-making process, it is still crucial for researchers to work with patients’ legal guardians and they should always respect any sort of advanced directives made by patients before they lost capacities. However, when it comes to the moment of the patient becoming incompetent to make informed choices, it surely will add burden to their legal guardians because there is no one size fits all pattern and more importantly, being a patient’s legal guardian does not mean that one knows exactly what the patient wants or what is the most favorable for the patient. Another important issue is the risk of secondary findings. With the aid of the most current technological advancements in genetic testing and brain imaging research, researchers now have access to more information about research participants than ever before. It is possible that through the course of the studies, researchers might uncover some genetic or brain anomalies which are not relevant to the research itself but potentially hazardous to the participants’ health. Therefore, it is crucial for researchers and the IRB, the Institutional Review Boards, to clearly define and communicate the policies about the discovery and reporting of these secondary findings. Last but not the least, the privacy and data sharing is considered essential in today’s science world. However, for Alzheimer’s research, we need a better way to balance the protection of research participants’ privacy and the sharing of data among researchers. While the national Alzheimer’s plan in the United States has called for the improvement of data sharing infrastructure, the researchers also need to take some measure to maximize the scientists’ ability to share and use data while protecting the privacy and autonomy of research participants. This balance is not only a significant challenge today but it will also be an ongoing challenge as technology continues to develop.

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