The Fisher Center Foundation funds scientists who continue to be at the forefront of research into the understanding of beta amyloid, a protein that is at the root of Alzheimer's disease. Beta amyloid forms dense protein deposits called plaques. Sometimes compared to tiny scouring pads, these beta amyloid plaques accumulate in the spaces between brain cells, choking them off and causing them to die Fisher Center scientists were among the first to define the specific steps by which beta amyloid is produced, and their discovery that pharmacological substances can interrupt this process set off a worldwide race to develop drugs to inhibit beta amyloid buildup. The Foundation's beta amyloid research is now focused on a protein called amyloid precursor protein (APP). When broken down in a certain way, APP results in the formation of beta amyloid plaque. Fisher scientists are unravelling the process by which APP processing is regulated. There immediate goal is to develop ways to slow the accumulation of plaque and other forms of beta amyloid in the brain and reduce their toxic effects on nerve cells, moving much closer to a cure for Alzheimer's disease. In fact, Fisher Center Foundation scientists are making significant progress in developing therapies aimed at reducing the production of toxic beta-amyloid, an achievement that will ultimately prevent, slow or even cure the disease. Fisher scientists recently identified several proteins that regulate the amount of beta-amyloid produced in the brain. What’s new is that these “regulator” proteins exert control over one or both of the enzymes that are known to produce beta-amyloid directly. Discovery of this “molecular fine-tuning” mean that Fisher scientists can now search for, or design, new drugs for treating Alzheimer’s.
Fisher scientists have also recently discovered how beta-amyloid damages communication between brain cells and how fibers connecting brain cells can be grown or made to shrink. With this understanding, it may be possible to devise therapies that protect the brain even when beta-amyloid production goes awry.
Most Alzheimer's disease patients show some signs of agitation and as Alzheimer's disease progresses through its later stages, as many as 75% of patients begin to exhibit aggressive or agitative behaviors, which are often treated with potent antipsychotic drugs. While useful, these drugs may cause incapacitating side effects. Building on two decades of research, Fisher Center Foundation scientists are exploring the mechanisms by which these antipsychotic drugs work in an effort to develop new and safer "anti-agitation" therapies that will improve the quality of life for patients while easing the burden on caregivers.
The devastating loss of memory that is the hallmark of Alzheimer's disease is caused by the death of nerve cells "strangled" by beta amyloid. In what would have seemed like science fiction a decade ago, the Foundation's scientists are making progress in reversing this damage by actually inducing nerve cells to grow new connections with other cells, thus improving communication between remaining healthy cells. This work builds on Fisher Foundation scientists' recent discovery that a protein called "WAVE1" regulates the growth of structures called spines that ultimately connect nerve cells, the Foundation's scientists are exploring ways to compensate for the death of nerve cells in Alzheimer's. These techniques might some day not only reverse symptoms such as memory loss in Alzheimer's patients, but might also treat other nervous system disorders such as Parkinson's and Huntington's disease, strokes, head trauma and spinal cord injuries.
The brains of people with Alzheimer’s contain large numbers of plaques and tangles. Plaques are formed from beta-amyloid. Tangles are made of a protein called tau. Like beta-amyloid, tangles can also damage the brain and thus contribute to the devastating loss of mental function in Alzheimer’s disease. Scientists have known for a while that tangles are caused when the tau protein does not fold properly. All proteins need to fold to have normal function. When a protein does not fold properly, it not only loses its own function, but also may damage many other proteins in cells, especially in the brain. Fisher scientists recently discovered that they could prevent the formation of tangles in a model of Alzheimer’s disease by supplying a drug that blocks a type of protein known as a “chaperone” or “stress protein.” This could lead to treatments that prevent much of the devastating damage to brain cells that occurs in Alzheimer’s. Such treatment might be applied along side an anti-amyloid treatment and this combination may turn out to be especially beneficial.
While being diagnosed with Alzheimer's can be overwhelming at any age, it is particularly devastating when the disease strikes early in one's life. Early-onset Alzheimer's can present itself in people as young as 30 and it is strongly inherited, affecting generation after generation. It is known that certain genetic mutations alter a set of proteins in the brain called "presenilins" and these alterations in turn lead to increased production of a toxic form of beta amyloid. Research funded by the Foundation recently shed light on the particular roles of three presenilin-associated proteins, nicastrin, PEN2 and APH1, which are involved in critical steps in the onset of Alzheimer's. Foundation scientists are also continuing to research the two presenilin proteins, PS1 and PS2, which are cause of most cases of early-onset Alzheimer's. Understanding the exact roles of PS1, PS2, PEN2, APH1 and nicastrin proteins in the development of Alzheimer's is a crucial step in developing therapies and drugs to slow or reverse the progression of the disease.
While searching for the cause and developing a cure for Alzheimer's disease, the Foundation is also funding projects to support the many family members and friends who are on the front lines of caring for the more than 5 million Alzheimer's patients in the US and beyond. Despite the massive burden of coping with a long list of patients' behavioral problems, such as aggressiveness and anxieties, little information is available for caregivers about effective treatments and interventions.
The Foundation funds research at the Fisher Alzheimer's Disease Education and Resources Program at New York University School of Medicine under the direction of Dr. Barry Reisberg. This research has led to the development of a new science of management for Alzheimer's and other dementias. Our next challenge is to raise funds to implement a caregiver training program based on this research and management principles. This program allows Alzheimer's patients to regain basic skills of daily living and reduces the patient's dependence on a caregiver, thus improving the quality of life for all involved.
In addition to numerous research projects, the Foundation also funds the Alzheimer's Information Program, which provides timely, accurate and reliable information to the general public through a number of tools.
The Foundation underwrote the production and distribution of a documentary entitled "Alzheimer's: Is Their Hope?" that provides an overview of the disease and introduces viewers to patients, caregivers and researchers battling Alzheimer's. Since it first aired in November 2002, the program has been shown on more than 60 public television stations in hundreds of communities across the US.
In November 2002, the Foundation launched the website www.ALZinfo.org, which has been recognized by doctors, caregivers, professional organizations, and the general public as the premier resource on Alzheimer's disease. Users are able to access a vast array of information through a single, easy to navigate source.
Dr. Paul Greengard
Director of the Fisher Center for Alzheimer's Disease Research at The Rockefeller University
Dr. Paul Greengard was awarded the year 2000 Nobel Prize in Physiology or Medicine for his pioneering work in delineating how neurons communicate with one another in the brain. During a half-century of research, he has been lauded for his singular contribution to our understanding of the complex signaling process that occur within each of the 100 billion or more nerve cells in the human brain. He is the Vincent Astor Professor at The Rockefeller University and Director of the Fisher Center laboratory. Dr. Greengard is also a member of the National Academy of Sciences and has received more than 50 awards and honors throughout his career. He has authored nearly 1000 scientific publications.
Professor of Psychiatry at New York University School of Medicine Clinical Director of the Aging and Dementia Research Center of the NYU School of Medicine
Dr. Reisberg has directed research over the past quarter century which has significantly advanced the current understanding and treatment of Alzheimer's disease. He was the first to describe many of the most important symptoms of Alzheimer's and the characteristic clinical course of the disease with the Global Deterioration Scale in 1982 and the Functional Assessment Staging measure in 1984.
Dr. William J. Netzer
Research Associate at the Fisher Center for Alzheimer's Research Foundation, and Scientific Liaison to the Fisher Foundation
Dr. Netzer's research led to the recent discovery that Gleevec, a successful anti-cancer drug, lowers beta-amyloid production, suggesting that Gleevec or compounds similar to it might be useful in treating Alzheimer's disease.
Assistant Professor of Neurological Surgery; Director, Center for Stereotactic & Functional Neurosurgery; and Director, Laboratory of Molecular Neurosurgery Weill Medical College of Cornell University
Dr. Kaplitt is a Tara and Victor Menezes Clinical Scholar in Neurological Surgery. He specializes in Parkinson's disease, Tremors and Movement Disorders. Dr. Kaplitt has completed the first phase 1 human clinical protocol of gene therapy for Parkinson's disease; expansion of this study is currently in preparation.
Sr. Research Associate at the Fisher Center for Alzheimer's Research Foundation
Dr. Flajolet’s research led to the recent discovery that a protein called “casein kinase one” regulates the production of beta-amyloid in the brain, suggesting that inhibitors of this protein might be useful in treating Alzheimer’s disease.
Research Associate at the Fisher Center for Alzheimer's Research Foundation
Dr. Luo’s research led to the recent discovery that the formation of tau tangles could be prevented by using a drug that reduces the activity of a protein called a “chaperone,” suggesting that this drug or compounds related to it could be used to treat the degeneration of brain cells in Alzheimer’s disease.
Post doctoral fellow at the Fisher Center for Alzheimer's Research Foundation
Dr. Schaefer’s research led to the discovery that molecules called “micro RNAs” (produced in the brain) are necessary to maintain normal brain development and function, suggesting that these molecules might be harnessed to treat Alzheimer’s disease.