With our aging population comes an ever-increasing incidence of Alzheimer’s disease (AD), and other age-related dementias. By the year 2050, there is forecast to be more than 13 million people living with AD in the USA, and new treatments are desperately needed to prevent this impending epidemic. There are currently no effective therapies for AD, with current clinical trials all attempting to directly target amyloid beta (Aβ) peptides thought to be the driver of neuronal degeneration. In the long term, scientists believe that we may have to use cocktails of drugs to effectively slow the disease, much as we now do for diseases such as HIV/AIDS. A new concept in AD research is that cellular processes regulating protein turnover (ie, the balance between protein synthesis and protein degradation) could be manipulated to prevent the build-up of the toxic Aβ peptides that cause neurological failure. In this work, we will be developing novel small molecules and peptides that we hope will enhance this protein turnover in neurons, and provide a starting point for designing new AD drugs.
See what research we fund.
- Brett Collins, PhDThe University of Queensland (Brisbane, Queensland, Australia)ID:A2018627SJuly 18, 2018Alzheimer'sStandard$191,034
- Celeste Karch, PhDWashington University School of Medicine (Saint Louis, MO)
Several lines of evidence suggest that inflammation and altered function of the cell types in the brain involved in inflammation, such as microglia, represent an early and critical driver of Alzheimer’s disease (AD). Our group has recently shown that a chemokine receptor type 4 (CXCR4) found in the cell types that mediate inflammation in the brain, such as microglia, contributes to tauopathies, such as progressive supranuclear palsy, frontotemporal dementia, corticobasal degeneration, and AD. The objective of this study is to begin to determine how CXCR4 drives AD. Together, the findings from this study will define the function of a new gene that increases risk for AD and other tauopathies and will shed light on its role in disease processes.ID:A2018349SJuly 1, 2018 to June 30, 2021Alzheimer'sStandard$300,000
- William Scott, PhDUniversity of Miami, Miller School of Medicine (Miami, FL)
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older adults in the United States. The factors that determine progression from early AMD (with little vision loss) to advanced AMD (with more severe vision loss) are poorly understood. We will use detailed clinical examinations of the eye and large-scale genetic analysis to identify new genetic factors that are associated with changes in the eye over time and with development of advanced AMD. The results of this study will improve our understanding of the AMD disease process and provide potential avenues for development of targeted therapies.ID:M2018112Co-principal Investigators:Margaret A. Pericak-Vance, PhDCollaborators:Jonathan L. Haines, PhD; Stephen G. Schwartz, MD; Jaclyn L. Kovach, MD; SriniVas Sadda, MDJuly 1, 2018 to June 30, 2020Macular DegenerationStandard$160,000
This grant is made possible by support from Dr. H. James and Carole Free.
- Magali Saint-Geniez, PhDThe Schepens Eye Research Institute, Harvard Medical School (Boston, MA)
Vision loss in AMD is caused by the dysfunction and loss of the retinal pigment epithelium (RPE), a pigmented layer of cells which support the photosensitive photoreceptors. RPE health and protective functions depend on their metabolism, the highly regulated process controlling energy production and by-products detoxification. Here we will study a novel pathogenic mechanism responsible for impaired RPE metabolism and progression to the advanced neovascular form of AMD.ID:M2018064July 1, 2018 to June 30, 2020Macular DegenerationStandard$160,000
- Farid Rajabli, PhDUniversity of Miami, Miller School of Medicine (Coral Gables, FL)
The strongest risk gene identified for Alzheimer disease (AD) is APOE. However, this gene does not increase the risk for AD in every ethnic population. For example, individuals with an African ethnic background do not seem to be very affected by this variation. This is due to the fact that individuals from different races/ethnicities harbor genetic differences at the site of the APOE gene. This is why it is important to study populations separately and to take into account their genetic background, also called local ancestry, when analyzing the genetic effect on the disease. We propose to explore the relationship between local ancestry of African-American and Caribbean-Hispanic people and AD risk genes. We will facilitate the discovery of ethnic-specific genes and genetic changes increasing the risk for AD. This approach will allow us to move a further step toward personalized and precision medicine.
ID:A2018556FMentors:Margaret A. Pericak-Vance, PhD; Gary W. Beecham Jr., PhDJuly 1, 2018 to June 30, 2020Alzheimer'sPostdoctoral Fellowship$150,000
- Jessica Young, PhDUniversity of Washington School of Medicine (Seattle, WA)
Alzheimer's disease (AD) is a devastating neurodegenerative disorder that is the most common cause of dementia in the elderly and is a tremendous socioeconomic burden. Stem cells derived from human patients can help us discover new therapeutics for AD because individual genetic background is captured in a dish and stem cells can be differentiated into neurons, a relevant cell type to analyze molecular features. My proposal will test whether genes identified with AD risk confer measurable laboratory read-outs characteristic of AD in neurons grown in the laboratory. In particular, I will focus on a particular cellular pathway, the endosomal network, which may become dysfunctional in AD before amyloid and tau deposition are reported.ID:A2018656SCollaborators:Suman Jayadev, MDJuly 1, 2018 to June 30, 2021Alzheimer'sStandard$300,000
- Ottavio Arancio, MD, PhDColumbia University (New York, NY)
The cognitive and behavioral symptoms that characterize Alzheimer’s disease (AD) are thought to result from impaired communication between neurons in the brain at connections called synapses. Toxic forms of a protein called tau play a central role in AD and other neurodegenerative conditions, and recent data show that tau can interfere with synapses in multiple ways. These observations greatly underscore efforts to treat AD by blocking the pathological actions of tau. The goal of this project is to better understand how tau interferes with synaptic function so that we can develop effective strategies to block the impairments it causes.ID:A2018816SCo-principal Investigators:Russell Nicholls, PhDJuly 1, 2018 to June 30, 2021Alzheimer'sStandard$300,000
- Jeffery Vance, MD, PhDUniversity of Miami (Miami, FL)
ApoE is a gene that is the strongest risk factor for Alzheimer disease (AD), but African carriers of the risk form of ApoE get AD less frequently than European carriers of the same form of the gene. We have localized the area on the chromosome that contains the DNA change that is lowering the risk for AD in Africans. By using DNA sequence data from different populations, comparing the sequence differences, and then seeing how the differences affect DNA function, we will create a small list of potential "protective" changes, changes that can be tested in biological models. The purpose is to identify how the protective DNA change works in Africans, and use that information to develop a drug to reduce the risk to get AD.ID:A2018425SCo-principal Investigators:Margaret Pericak-Vance, PhD; Gary Beecham, PhD; Anthony Griswold, PhDJuly 1, 2018 to June 30, 2021Alzheimer'sStandard$300,000
- Xiangrun Huang, PhDUniversity of Miami, Miller School of Medicine (Miami, FL)
Glaucoma, a leading cause of blindness worldwide, damages a type of neuronal cells called retinal ganglion cells and their nerve fibers, known as axons, in the eye. Early detection of abnormities of the nerve fibers can permit early medical intervention to prevent vision loss in glaucomatous patients. The proposed research will develop a new optical imaging method that detects abnormities of the light reflected by the nerve fibers. The new approach can provide sensitive detection of the abnormities that occur at early stages of glaucoma. If successful, the developed methods can be readily translated to clinical use and provide clinicians with a new means to sensitively detect early glaucomatous damage, opening an early therapeutic window for the prevention of glaucomatous damage and vision loss.ID:G2018148July 1, 2018 to June 30, 2020GlaucomaStandard$150,000
The Dr. Douglas H. Johnson Award recipient
- Biji Mathew, PhDUniversity of Illinois at Chicago (Chicago, IL)
Retinal ganglion cell death and axonal loss are hallmark events leading to glaucoma and neuroprotection of retina by regeneration, or prevention of cells from dying, are key factors and major public health necessities. Our objective is to study the use of extracellular vehicles (EVs), tiny particles secreted by mesenchymal stem cells, as a treatment for glaucoma induced cell death. Delivering the EVs specifically in to the retina and prolonging the effect, are major limitations reducing the treatment efficacy. Therefore, our study is focused on engineering modified targeted EVs for retina -specific neuroprotective action for treating glaucoma.ID:G2018168July 1, 2018 to June 30, 2020GlaucomaStandard$150,000