Alzheimer's Disease: Life's Basics Rewind
Alzheimer’s Disease: Life’s Basics Rewind
An infant learns life’s basics one at a time: how to eat, eliminate, vocalize, recognize, remember, move muscles, and express emotions. Sadly, an Alzheimer’s patient, like a rewinding video image of learning, loses such basic life skills sequentially.
More than 5 million Americans suffer from Alzheimer’s disease (AD). It is the sixth leading cause of death and the only fatal disease in our nation that is getting worse, not better. The costs of caring for patients during their deadly downward spiral is more than $100 billion annually, making it the third most costly illness after heart disease and cancer. Several drugs moderate AD symptoms, but none slow its progression or cure it.
Wide ranging benefits to patients, their families, and to our society at large only can come from focused, groundbreaking laboratory science innovations such as those currently on Georgetown University Medical Center’s (GUMC) integrated, scientific research agenda. The medical center’s approach is designed to understand what causes disease onset and progression so that early intervention – including conventional and novel therapies--can staunch the disease before the patient deteriorates.
The Brain and Life Diminish
The earliest warning signs of the onset of AD involve memory processing. Examples include repeatedly forgetting ordinary things and losing oneself in familiar places, acute confusion, and poor judgment. In one laboratory study, for example, rats with AD, used to swimming in a pool with islands where they could rest, repeatedly forgot where the islands were located and swam to the point of exhaustion.
To compensate and to avoid embarrassment, people with early AD symptoms may quit a favorite activity such as golf or cards and withdraw from other people for fear these changes will be noticed. Often, early AD can look a lot like depression or anxiety.
In healthy brains, proteins are broken down and eliminated. But in AD, plaques of insoluble beta amyloids -- proteins --form. The accumulation of these plaques outside of the cells triggers a sort of cluttering process that chokes off cells and diminishes brain tissue. In the cerebral cortex, as brain matter decreases, spaces in the brains’ folds – sulci – enlarge, reversing cognition and sharpening the decline.
As the disease progresses, proteins form twisted, insoluble fibers called neurofibrillary tangles inside of cells where they collapse the cell structure. This process starts in the deep limbic region of the basal forebrain, where memory resides
The brain, literally, is shrinking.
The AD patient’s present brain function is like a tape machine that plays but no longer can record. Eventually, it no longer can play, either: combativeness, incontinence, and wandering increase. Groans and moans overshadow speech. A vacant look replaces facial expressions. Diapers replace use of the bathroom. Patients, like infants, must be fed, clothed, and constantly monitored. The body grows increasingly weak. Illnesses such as pneumonia frequently kill frail AD patients.
While we think of AD as a disease of the elderly, postmortem evidence shows that pathological hallmarks of AD appear much earlier than the first outward signs, such as short term memory loss. To learn more about lifestyle choices you can make to reduce your risk of Alzheimer’s Disease go to http://gumc.georgetown.edu/news/36625.html
Extraordinary Research on Alzheimer’s at GUMC
The very core of GUMC’s renowned strengths – the education of physicians, nurses and scientists, its laboratory research and clinical trials, is systems medicine, an integrated approach that factors in a patient’s genetic history and make up as well as myriad environmental factors specific to the individual’s life.
The goal of this approach is to detect the potential for illness early and begin lifestyle and therapeutic steps to delay the onset of symptoms, dampen down the disease, or stem it altogether. In more than nine out of every ten patients genetic and environmental factors combine to trigger “sporadic” or late onset AD. Only a small fraction of cases are caused by genetic mutations alone.
At GUMC, scientists are studying all levels of Alzheimer’s disease and its possible triggers from the molecular to the mundane: What cellular and basic biological changes occur, when and why? What is the impact of lifestyle choices such as smoking, drinking, and exercise? What about life events such as head injuries and duration of education?
In general, factors that raise the risk of heart disease have been linked to increased risk of AD. Obesity, high blood pressure, high cholesterol, diabetes are all risk factors. Under the systems medicine approach, healthcare from infancy to old age would focus on reducing these risks. Research would focus on understanding the mechanisms of their risk, and developing therapeutics to treat the diseases. To learn what you personally can do to reduce your risk of Alzheimer's, go to http://gumc.georgetown.edu/news/36625.html
The Memory Disorders Program in the Department of Neuroscience is a national leader in the research and testing of new drugs and vaccines for AD. In partnership with MedStar’s GU Hospital, the program provides care to more than 1,500 patients, many of them participants in clinical trials and research studies. The program manages multiple industry and NIH-funded clinical trials evaluating new treatments for Alzheimer’s disease and is recruiting for numerous other studies. For an in-depth look at MDP, go to: http://gumc.georgetown.edu/news/42066.html. For an in-depth look at one AD Clinical Trial, go to: http://gumc.georgetown.edu/news/36626.html
Research Leaders and Leading Research
Howard J. Federoff, MD, Ph.D., Executive Vice President for Health Sciences, Executive Dean for the School of Medicine, and professor, department of neurology, is a highly accomplished scientist whose research focuses on gene therapy and neurodegenerative diseases including Alzheimer’s and Parkinson’s Disease. His work seeks to define the underlying molecular and/or cellular principles that allow for dissection of potential pathogenic processes and then to exploit this information to develop preclinical therapeutic strategies, moving the most promising to early stage clinical trials. Studies include amplicon-based vaccination for AD, development of an HIV vaccine strategy based on the HSV-1 amplicon vector, and proteomic biomarkers from leukocytes and gene therapy for Parkinson's disease patients. Dr. Federoff holds numerous patents, has published extensively and serves on the editorial boards of five leading peer-reviewed journals and is founding scientist of several biotech companies. He also serves as Chair of the NIH Recombinant DNA Advisory Committee. For more about Dr. Federoff, go to , http//gumc.georgtown.edu/news/20935.html.
R. Scott Turner, MD, Ph.D., professor, department of neurology and Director, Memory Disorders Program., is an expert in the diagnosis and treatment of people with memory disorders. Turner directs federal and foundation-funded research projects to study cognitive disorders, Alzheimer's disease and its basic mechanisms, and clinical studies of neurodegenerative dementias. Turner’s basic research includes studies of passive immunization of a mouse model of AD. His clinical research includes the role of DHA, a type of omega-3 fatty acid found in fish and walnuts, and its effect on the production and protection of brain cells against the harmful effects of amyloid protein that would slow the progression of memory loss; the regulation of the amyloid precursor protein (APP) breakdown that could lead to new therapeutic targets including a potential gene-therapy approach; and a trial to evaluate the impact of resveratrol treatment, a compound that promotes neuronal survival, on AD biomarkers and on patients with mild to moderate Alzheimer’s disease. Turner has published his research in neurodegenerative dementias in both basic and clinical research journals. To learn more about Turner go to: http://gumc.georgetown.edu/news/34932.html and to www.memory.georgetown.edu
G. William Rebeck, Ph.D., associate professor of neuroscience and a member of the Center for Neural Injury and Recovery at Georgetown, has been studying genetic risk factors for Alzheimer’s disease for 15 years. The strongest genetic risk factor for AD is APOE. Known to encode a protein in cholesterol transport to the blood and the brain, which can increase the accumulation of plaques in the brain, its function in the brain is still not well understood. One form of the gene –APOE epsilon 4—increases vulnerability to sporadic AD. Rebeck’s research shows that a pair of APOE ε4 genes appears to signal an almost certain victim of AD, a finding that has helped explain the nature of family history in Alzheimer’s, and is leading to new therapeutic approaches.
Dr. Rebeck and his lab of post-doctoral fellows, graduate students, and undergraduates are examining ways of interfering with this process to diminish the negative effects of the gene and high cholesterol. This research is also having interesting implications for how the brain responds to other types of damage, such as traumatic brain injury. Dr. Rebeck has received numerous peer-reviewed grants from the NIH to explore basic mechanisms of Alzheimer’s disease and published over 90 peer-reviewed articles related to Alzheimer’s disease.
To learn more about Rebeck’s AD research go to: http://gumc.georgetown.edu/news/68114.html
Mark Burns, PhD, assistant professor, department of neuroscience, is investigating the role of cholesterol in the development of AD. He and his researchers found that cholesterol lowering therapies, such as statin drugs, more than cut in half the production of toxic proteins that hallmark AD. He is also examining the mechanism behind the observations that head injury can increase the risk of AD.
Hyang-Sook Hoe, PhD, assistant professor, department of neuroscience, is investigating how the apoE protein affects the formation and stability of synapses in the brain. She has identified mechanisms for reversing the neuronal deficits seen in individuals with APOE ε4, and is pursuing new therapeutic approaches to AD in mouse models.
Tim Mhyre, Ph.D., assistant professor, department of neuroscience, studies alterations in peripheral immune cells in neurological disorders, including Alzheimer’s and Parkinson’s disease. His team uses this knowledge to develop clinical biomarkers that will help diagnose and stage the disease and even help in the discovery of curative drugs. The researchers examine how genes, biological molecules, and different proteins in blood influence disease risk. One goal is to create an archive of high quality human samples, an important resource for future work on disease processes--injury, repair, and therapies. Researchers can combine the technologies, methodologies, and economies-of-scale necessary to analyze high-dimensional biological data and mine these samples to diagnose, track and treat neurodegenerative disease.
Pamela Saunders, Ph.D., assistant professor, department of neurology, is a socio-linguist and an expert on communication issues in dementia care. A pilot program with 11 Jesuit patients is underway to gather data on educational history and challenges, religious and spiritual beliefs, physical activity, and childhood experiences, among other areas. This collaboration with the Jesuit community is enhanced by the rich lifelong context that includes writing samples from their religious experiences.
Saunders also studies communication, aging, and Alzheimer’s disease. She has written several articles on doctor-patient communications among older patients. In addition, Saunders is working with medical students to improve their skills in communicating with older patients.
Periodic briefings on their studies and experiments, followed by tours of their laboratories, are available to the public. To learn more about and sign up for such a tour, contact the office of Medical Center Advancement at 202-687-6561 or email MedCenterAdvancement@georgetown.edu.
An infant learns life’s basics one at a time: how to eat, eliminate, vocalize, recognize, remember, move muscles, and express emotions. Sadly, an Alzheimer’s patient, like a rewinding video image of learning, loses such basic life skills sequentially.
More than 5 million Americans suffer from Alzheimer’s disease (AD). It is the sixth leading cause of death and the only fatal disease in our nation that is getting worse, not better. The costs of caring for patients during their deadly downward spiral is more than $100 billion annually, making it the third most costly illness after heart disease and cancer. Several drugs moderate AD symptoms, but none slow its progression or cure it.
Wide ranging benefits to patients, their families, and to our society at large only can come from focused, groundbreaking laboratory science innovations such as those currently on Georgetown University Medical Center’s (GUMC) integrated, scientific research agenda. The medical center’s approach is designed to understand what causes disease onset and progression so that early intervention – including conventional and novel therapies--can staunch the disease before the patient deteriorates.
The Brain and Life Diminish
The earliest warning signs of the onset of AD involve memory processing. Examples include repeatedly forgetting ordinary things and losing oneself in familiar places, acute confusion, and poor judgment. In one laboratory study, for example, rats with AD, used to swimming in a pool with islands where they could rest, repeatedly forgot where the islands were located and swam to the point of exhaustion.
To compensate and to avoid embarrassment, people with early AD symptoms may quit a favorite activity such as golf or cards and withdraw from other people for fear these changes will be noticed. Often, early AD can look a lot like depression or anxiety.
In healthy brains, proteins are broken down and eliminated. But in AD, plaques of insoluble beta amyloids -- proteins --form. The accumulation of these plaques outside of the cells triggers a sort of cluttering process that chokes off cells and diminishes brain tissue. In the cerebral cortex, as brain matter decreases, spaces in the brains’ folds – sulci – enlarge, reversing cognition and sharpening the decline.
As the disease progresses, proteins form twisted, insoluble fibers called neurofibrillary tangles inside of cells where they collapse the cell structure. This process starts in the deep limbic region of the basal forebrain, where memory resides
The brain, literally, is shrinking.
The AD patient’s present brain function is like a tape machine that plays but no longer can record. Eventually, it no longer can play, either: combativeness, incontinence, and wandering increase. Groans and moans overshadow speech. A vacant look replaces facial expressions. Diapers replace use of the bathroom. Patients, like infants, must be fed, clothed, and constantly monitored. The body grows increasingly weak. Illnesses such as pneumonia frequently kill frail AD patients.
While we think of AD as a disease of the elderly, postmortem evidence shows that pathological hallmarks of AD appear much earlier than the first outward signs, such as short term memory loss. To learn more about lifestyle choices you can make to reduce your risk of Alzheimer’s Disease go to http://gumc.georgetown.edu/news/36625.html
Extraordinary Research on Alzheimer’s at GUMC
The very core of GUMC’s renowned strengths – the education of physicians, nurses and scientists, its laboratory research and clinical trials, is systems medicine, an integrated approach that factors in a patient’s genetic history and make up as well as myriad environmental factors specific to the individual’s life.
The goal of this approach is to detect the potential for illness early and begin lifestyle and therapeutic steps to delay the onset of symptoms, dampen down the disease, or stem it altogether. In more than nine out of every ten patients genetic and environmental factors combine to trigger “sporadic” or late onset AD. Only a small fraction of cases are caused by genetic mutations alone.
At GUMC, scientists are studying all levels of Alzheimer’s disease and its possible triggers from the molecular to the mundane: What cellular and basic biological changes occur, when and why? What is the impact of lifestyle choices such as smoking, drinking, and exercise? What about life events such as head injuries and duration of education?
In general, factors that raise the risk of heart disease have been linked to increased risk of AD. Obesity, high blood pressure, high cholesterol, diabetes are all risk factors. Under the systems medicine approach, healthcare from infancy to old age would focus on reducing these risks. Research would focus on understanding the mechanisms of their risk, and developing therapeutics to treat the diseases. To learn what you personally can do to reduce your risk of Alzheimer's, go to http://gumc.georgetown.edu/news/36625.html
The Memory Disorders Program in the Department of Neuroscience is a national leader in the research and testing of new drugs and vaccines for AD. In partnership with MedStar’s GU Hospital, the program provides care to more than 1,500 patients, many of them participants in clinical trials and research studies. The program manages multiple industry and NIH-funded clinical trials evaluating new treatments for Alzheimer’s disease and is recruiting for numerous other studies. For an in-depth look at MDP, go to: http://gumc.georgetown.edu/news/42066.html. For an in-depth look at one AD Clinical Trial, go to: http://gumc.georgetown.edu/news/36626.html
Research Leaders and Leading Research
Howard J. Federoff, MD, Ph.D., Executive Vice President for Health Sciences, Executive Dean for the School of Medicine, and professor, department of neurology, is a highly accomplished scientist whose research focuses on gene therapy and neurodegenerative diseases including Alzheimer’s and Parkinson’s Disease. His work seeks to define the underlying molecular and/or cellular principles that allow for dissection of potential pathogenic processes and then to exploit this information to develop preclinical therapeutic strategies, moving the most promising to early stage clinical trials. Studies include amplicon-based vaccination for AD, development of an HIV vaccine strategy based on the HSV-1 amplicon vector, and proteomic biomarkers from leukocytes and gene therapy for Parkinson's disease patients. Dr. Federoff holds numerous patents, has published extensively and serves on the editorial boards of five leading peer-reviewed journals and is founding scientist of several biotech companies. He also serves as Chair of the NIH Recombinant DNA Advisory Committee. For more about Dr. Federoff, go to , http//gumc.georgtown.edu/news/20935.html.
R. Scott Turner, MD, Ph.D., professor, department of neurology and Director, Memory Disorders Program., is an expert in the diagnosis and treatment of people with memory disorders. Turner directs federal and foundation-funded research projects to study cognitive disorders, Alzheimer's disease and its basic mechanisms, and clinical studies of neurodegenerative dementias. Turner’s basic research includes studies of passive immunization of a mouse model of AD. His clinical research includes the role of DHA, a type of omega-3 fatty acid found in fish and walnuts, and its effect on the production and protection of brain cells against the harmful effects of amyloid protein that would slow the progression of memory loss; the regulation of the amyloid precursor protein (APP) breakdown that could lead to new therapeutic targets including a potential gene-therapy approach; and a trial to evaluate the impact of resveratrol treatment, a compound that promotes neuronal survival, on AD biomarkers and on patients with mild to moderate Alzheimer’s disease. Turner has published his research in neurodegenerative dementias in both basic and clinical research journals. To learn more about Turner go to: http://gumc.georgetown.edu/news/34932.html and to www.memory.georgetown.edu
G. William Rebeck, Ph.D., associate professor of neuroscience and a member of the Center for Neural Injury and Recovery at Georgetown, has been studying genetic risk factors for Alzheimer’s disease for 15 years. The strongest genetic risk factor for AD is APOE. Known to encode a protein in cholesterol transport to the blood and the brain, which can increase the accumulation of plaques in the brain, its function in the brain is still not well understood. One form of the gene –APOE epsilon 4—increases vulnerability to sporadic AD. Rebeck’s research shows that a pair of APOE ε4 genes appears to signal an almost certain victim of AD, a finding that has helped explain the nature of family history in Alzheimer’s, and is leading to new therapeutic approaches.
Dr. Rebeck and his lab of post-doctoral fellows, graduate students, and undergraduates are examining ways of interfering with this process to diminish the negative effects of the gene and high cholesterol. This research is also having interesting implications for how the brain responds to other types of damage, such as traumatic brain injury. Dr. Rebeck has received numerous peer-reviewed grants from the NIH to explore basic mechanisms of Alzheimer’s disease and published over 90 peer-reviewed articles related to Alzheimer’s disease.
To learn more about Rebeck’s AD research go to: http://gumc.georgetown.edu/news/68114.html
Mark Burns, PhD, assistant professor, department of neuroscience, is investigating the role of cholesterol in the development of AD. He and his researchers found that cholesterol lowering therapies, such as statin drugs, more than cut in half the production of toxic proteins that hallmark AD. He is also examining the mechanism behind the observations that head injury can increase the risk of AD.
Hyang-Sook Hoe, PhD, assistant professor, department of neuroscience, is investigating how the apoE protein affects the formation and stability of synapses in the brain. She has identified mechanisms for reversing the neuronal deficits seen in individuals with APOE ε4, and is pursuing new therapeutic approaches to AD in mouse models.
Tim Mhyre, Ph.D., assistant professor, department of neuroscience, studies alterations in peripheral immune cells in neurological disorders, including Alzheimer’s and Parkinson’s disease. His team uses this knowledge to develop clinical biomarkers that will help diagnose and stage the disease and even help in the discovery of curative drugs. The researchers examine how genes, biological molecules, and different proteins in blood influence disease risk. One goal is to create an archive of high quality human samples, an important resource for future work on disease processes--injury, repair, and therapies. Researchers can combine the technologies, methodologies, and economies-of-scale necessary to analyze high-dimensional biological data and mine these samples to diagnose, track and treat neurodegenerative disease.
Pamela Saunders, Ph.D., assistant professor, department of neurology, is a socio-linguist and an expert on communication issues in dementia care. A pilot program with 11 Jesuit patients is underway to gather data on educational history and challenges, religious and spiritual beliefs, physical activity, and childhood experiences, among other areas. This collaboration with the Jesuit community is enhanced by the rich lifelong context that includes writing samples from their religious experiences.
Saunders also studies communication, aging, and Alzheimer’s disease. She has written several articles on doctor-patient communications among older patients. In addition, Saunders is working with medical students to improve their skills in communicating with older patients.
Periodic briefings on their studies and experiments, followed by tours of their laboratories, are available to the public. To learn more about and sign up for such a tour, contact the office of Medical Center Advancement at 202-687-6561 or email MedCenterAdvancement@georgetown.edu.
