Our team of internationally renowned scientists, under the direction of Nobel Laureate Dr. Paul Greengard until his death in 2019, has been at the forefront of seminal research that has provided a conceptual framework for modern day investigations into Alzheimer’s disease. Our groundbreaking research is the key to finding a cure for Alzheimer’s by advancing truly effective therapies that can arrest its development, or prevent the illness altogether.
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 Center’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 unraveling the process by which APP processing is regulated. Their 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.
Fisher Center 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” means 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 scientists are exploring the mechanisms by which these antipsychotic drugs work 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 Center’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 the Fisher Center scientists’ discovery that a protein called “WAVE1” regulates the growth of structures called spines that ultimately connect nerve cells. These techniques might someday 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 alongside 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. Fisher Center scientists are also continuing to research the two presenilin proteins, PS1 and PS2, which are the 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 6 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 many resources, including its website, ALZinfo.org. The website features a unique Research Locator that allows visitors to input their zip code to pinpoint doctors, nurses, disease centers, elder attorneys, Medicare information and home health agencies and more. The Foundation also provides a 1-800-ALZINFO phone system that assists people who do not have access to the Internet. Furthermore, caregivers can join our support group through our Caregiver’s Corner.
The Foundation’s award-winning tri-annual publication, Preserving Your Memory® circulates 52,000 copies per issue. The scientific staff at The Rockefeller University reviews the magazine’s editorial content for accuracy and solidity as it addresses concerns of readers affected by the disease—whether caregiver or patient—and provides information about Alzheimer’s treatment, care options, and how to take the necessary steps to adequately prepare if they receive an Alzheimer’s diagnosis.
The public can ask our researchers questions through Ask the Experts and sign up to receive our free online newsletter, Alzheimer’s Research News You Can Use, the most reviewed Alzheimer’s and dementia newsletter on the internet.
Lastly, ALZinfo.org offers a Memory Wall where the memory of loved ones can be memorialized by uploading photos, a bio and audio to treasure.