Sleep problems, such as wakefulness at night and daytime napping, are common in patients with Alzheimer disease (AD). While sleep disturbances are often considered to be a consequence of neurodegeneration, we are taking another look. Data suggest that sleep disturbances occur very early in the course of the disease and might possibly contribute to AD-associated pathologies as well as the onset of cognitive symptoms including mild cognitive impairment (MCI). By switching sleep on and off, we will be able to assess whether sleep disturbances, such as unusual sleep duration and sleep fragmentation, are an early factor that contributes to the risk of developing AD.
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- Sarah Fritschi, PhDWashington University School of Medicine (St. Louis, MO)ID:A2017114FMentors:David M. Holtzman, MDJuly 1, 2017 to September 30, 2018Alzheimer's DiseasePostdoctoral Fellowship$100,000
- Chadwick Hales, MD, PhDEmory University (Atlanta, GA)
Brain cells are made up of many different proteins that help them work correctly. Bad proteins can build up in the brain cells and cause them to become sick and die in Alzheimer’s disease. We want to study how a group of proteins known as ribonucleic acid (RNA) processing factors may cause bad proteins to build up in the cells. Results from the study may show us a new way to slow or stop the brain cell injury in Alzheimer’s disease (AD).ID:A2017281SCollaborators:Lary Walker, PhDJuly 1, 2017 to June 30, 2020Alzheimer's DiseaseStandard$300,000
- 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
- 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 Hyman, MD, PhDJuly 1, 2017 to June 30, 2019Alzheimer's DiseasePostdoctoral Fellowship$100,000
- 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
- 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
- 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
- Mar Hernandez-Guillamon, PhDVall de Hebron Research Institute (Barcelona, Spain)
Beta-amyloid (Aβ) protein accumulates abnormally in the Alzheimer’s brain, to a degree that is believed to be sufficient to induce neuronal cell death. Evidence suggests that the levels and distribution of lipids in the brain influence the transport and deposition of Aβ protein. The aim of this proposal is to determine the effect of a new treatment based on the administration of a natural modified protein that is able to mobilize lipids in a transgenic mouse model of AD. This protein, the ApoA-I-Milano variant, has been shown to be protective in cardiovascular diseases; however, its properties have never been tested in brain diseases.ID:A2017243SCollaborators:Lidia Giménez-Llort, PhD; Fabien Gosselet, PhDJuly 1, 2017 to June 30, 2020Alzheimer's DiseaseStandard$300,000
- Ephraim F. Trakhtenberg, PhDUniversity of Connecticut Health Center (Farmington, CT)
The biological molecular mechanisms controlling the growth of connections in the central nervous system (CNS) are still poorly understood. The inability of the eye to regenerate such connections to the brain is the key reason why vision is lost from optic nerve damage, which can happen in a disease such as glaucoma, cannot be restored. We propose to identify novel biological regulators of the intrinsic ability of the retinal cells to regrow such connections between the eye and the brain. These studies could lead to the development of therapeutics for restoring simple visual abilities to those who became blind due to angle-closure glaucoma, and possibly other types of glaucoma.ID:G2017204July 1, 2017 to June 30, 2019GlaucomaStandard$150,000
- Derek Welsbie, MD, PhDUniversity of California, San Diego (La Jolla, CA)
Nerve cells called retinal ganglion cells (RGCs) form the connection between the eye and the brain. In glaucoma, these nerve cells die and vision is permanently lost. We have previously shown that a protein called dual leucine zipper kinase (DLK) is critical for the death of these cells. Thus, this proposal seeks to develop a gene therapy vector that might interfere with DLK and prevent RGC death and accompanying vision loss.ID:G2017212Collaborators:Donald J. Zack, MD, PhDJuly 1, 2017 to June 30, 2019GlaucomaStandard$150,000
Recipient of the Dr. Douglas H. Johnson Award