My research aims to determine whether depletion of TAR DNA-binding protein 43 (TDP-43) in neurons contributes to pathological conversion of tau or accelerates tauopathy, a critical driver of neuron loss and cognitive decline in sporadic Alzheimer’s disease (AD). The pathological alteration and aggregation of tau protein (called tauopathy) is arguably the most important alteration in AD, as it shows the strongest association with the loss of brain cells and memory. Many studies have shown TDP-43 abnormality in 30-70% of AD cases, and that these cases show worsened memory loss. The aim of our study is to find out if TDP-43 loss plays a role in the initiation or acceleration of tauopathy in AD. Once we know what drives the changes in tau, we can halt or slow the progression of this disease.
See what research we fund.
- Resham Chhabra, PhDJohns Hopkins University (Baltimore, MD)ID:A2017102FMentors:Tong Li, PhD; Philip Wong, PhDJuly 1, 2017 to June 30, 2019Alzheimer's DiseasePostdoctoral Fellowship$100,000
- Linda Zangwill, PhDUniversity of California, San Diego
Numerous studies have suggested that vascular factors (blood supply) are involved in the development of glaucoma, but it is currently not known whether a reduction in blood supply to the eye is a cause or an effect of the glaucoma disease process. Recent advances in imaging technology have made it possible to visualize and measure the retinal blood supply, as well as assess the deep layers of the optic nerve head, including the lamina cribrosa, during routine eye exams. This prospective clinical research study will investigate whether changes in the retinal blood supply precede or follow other structural and mechanical changes in glaucoma.ID:G2017122Co-principal Investigators:Min Suh Hee, MDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000
- Daniel Bos, MD, PhDErasmus Medical Center (Rotterdam, Netherlands)
Atherosclerosis, or hardening of the arteries, is increasingly recognized as an important risk factor for dementia. Yet, it remains unclear whether the progression of atherosclerosis at different locations in the arterial system also contributes to changes in the structure or function of the brain, and ultimately to dementia. Knowledge of the dynamics of atherosclerosis and its role in brain changes will greatly improve our insight into the development of dementia. At a later point, this knowledge may even offer therapeutic or preventive opportunities to reduce the number of persons suffering from dementia by targeting atherosclerosis.ID:A2017424FJuly 1, 2017 to June 30, 2019Alzheimer's DiseasePostdoctoral Fellowship$98,823
- Ethan Lippmann, PhDVanderbilt University (Nashville, TN)
In patients with Alzheimer's disease (AD) and dementia, the blood vessels of the brain become leaky, which worsens symptoms like memory loss. We are trying to identify why these blood vessels become leaky. If we understand the cause of this leakage, we can potentially target it with new drugs to improve patient outcomes.ID:A2017094SCo-principal Investigators:Laura Dugan, MDJuly 1, 2017 to June 30, 2020Alzheimer's DiseaseStandard$300,000
- Sarah DeVos, PhDMassachusetts General Hospital/Harvard University (Boston, MA)
A major driver of Alzheimer’s disease (AD) is the accumulation of the protein tau that travels through the human brain in a constant pattern. Tau molecules become misshapen and aggregate in AD, though no one has yet identified how, or even if, these tau accumulations result in neuronal death. In this research, we have developed a fluorescent tool that will allow us to watch tau collect in neurons both in cell culture as well as the living adult mouse brain. Using this tool, this research aims to observe directly, in real time, what happens once a neuron develops a tau aggregate, as well as to study which genes increase or decrease in a neuron once it develops one of these tau accumulations. Together, these data will help us better understand the immediate changes that occur in adult neurons when they develop AD-like tau accumulations and may help identify new druggable pathways involved in the development of AD in human patients.
Note: This grant was terminated by the investigator in February of 2018 when she left Harvard University for an industry position.ID:A2017436FMentors:Bradley Hymen, MD, PhDJuly 1, 2017 to June 30, 2019Alzheimer's DiseasePostdoctoral Fellowship$100,000
- Sarah McFarlane, PhDUniversity of Calgary (Canada)
In neovascular age-related macular degeneration (AMD), the sprouting of new blood vessels (angiogenesis/neovascularization) leads to the death of the nerve cells of the retina. Neovascular AMD places a substantial burden on patients and the healthcare system. Current approaches to block new blood vessels from forming are not effective in many patients and they have serious side effects. There’s an urgent need for effective new ways to prevent these faulty new blood vessels from forming, but not affect the health of retinal nerve cells or the normal blood vessels. To address this need, we are developing a genetic animal model where we can rapidly identify novel, safe and effective drugs for the treatment of neovascular AMD.ID:M2017002July 1, 2017 to June 30, 2019Macular DegenerationStandard$123,160
- Terrance Kummer, MD, PhDWashington University School of Medicine (Saint Louis, MO)
The incredibly complex circuitry of the brain is the structural foundation of normal cognition. In Alzheimer’s disease (AD), these neural circuits begin to break down, leading to the hallmark cognitive decline of AD. This happens at many sites throughout the brain over many years, yet remains invisible to clinical imaging techniques like MRI until so advanced that it is likely irreversible. Our goal is to develop new MRI approaches that can reveal these microscopic circuit injuries in model systems and in patients suffering from AD. With such a technique in-hand, we will be far better positioned to understand and ultimately disrupt the pathways that lead to neural circuit injury in AD.ID:A2017084SCollaborators:ShiNung Ching, PhD; Joong-Hee Kim, PhDJuly 1, 2017 to June 30, 2020Alzheimer's DiseaseStandard$299,912
- Randy McIntosh, PhDBaycrest Centre for Geriatric Care (Toronto, Canada)
The brain is a complicated system whose different parts interact to support a variety of cognitive functions. This complexity makes it difficult to treat diseases such as Alzheimer’s and Parkinson’s, where many different brain areas can be affected, but lead to very similar deficits, such as memory dysfunction. Our research provides a framework of tools to “reconstruct” the brain and build models of different dementias to characterize the unique features of each disease and the final common paths to cognitive impairment. As our work progresses, it will be used to evaluate the potential of therapeutic interventions to help identify treatment targets, or areas of the brain that, if treated, are most likely to result in the best outcome for the individual.ID:A2017286SCo-principal Investigators:Kelly Shen, PhDCollaborators:Michael Breakspear, PhD; Viktor Jirsa, PhD; Petra Ritter, PhD; Ana Solodkin, PhDJuly 1, 2017 to June 30, 2020Alzheimer's DiseaseStandard$299,565
- Randall Bateman, MDWashington University School of Medicine (St. Louis, MO)
Alzheimer’s disease (AD) is a devastating neurological disease for which there currently are no effective therapeutics. Critical to the development of therapeutics that may treat and even cure AD is an understanding of the dynamics (the change over time) of certain amyloid-beta (Aβ) proteins that are a likely cause of AD in the human brain. We are using the most advanced imaging technology to answer these questions in patients in order to accelerate drug development and improve patient outcomes.ID:A2017081SCo-principal Investigators:Robert Schmidt, MD, PhD; Norelle C. Wildburger, PhDCollaborators:Frank Gyngard, PhD; Bruce Patterson, PhD; Matthew L. Steinhauser, MDJuly 1, 2017 to September 30, 2020Alzheimer's DiseaseStandard$300,000
- Ji Yi, PhDBoston Medical Center (Boston, MA)
Glaucoma is an eye disease that affects millions of American’s vision. The best way to slow and stop the disease is to detect it early; however, existing methods are insufficient to do so. We plan to develop a new optical imaging technology to examine the eye, which is very sensitive to early glaucoma so that we can use it for early diagnosis. This project not only may benefit many people by helping to prevent blindness, but also could enhance our understanding how this disease develops.ID:G2017077Collaborators:Manishi Desai, MDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000