Neuroinflammation in the brain may be caused in part by neurodegenerative diseases such as tauopathies and Alzheimer’s disease. The brain’s resident immune cells, called microglia, are the resident “garbage disposal cells” of the brain and thereby play key roles in any inflammatory processes. Using a novel multiscale computational approach, a team from Mount Sinai identified the protein Tyrobp as a causal regulator controlling the garbage disposal actions of microglia. To understand the role of Tyrobp in tauopathies, we generated new genetically-manipulated tauopathy-model mice that are rendered deficient for Tyrobp. Characterization of these mice will help to determine how Tyrobp modifies inflammation and the progression of tauopathy, thereby greatly influencing this field of research.
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- Mickael Audrain, PhDIcahn School of Medicine at Mount Sinai (New York, NY)ID:A2018253FMentors:Sam Gandy, MD, PhDJuly 1, 2018 to June 30, 2020Alzheimer's DiseasePostdoctoral 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's DiseaseStandard$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
- Joseph Castellano, PhDIcahn School of Medicine at Mount Sinai (New York, NY)
Possession of the APOE-ε4 gene confers a strong risk for earlier onset of Alzheimer’s disease (AD), a devastating brain disorder that damages brain synapses, or connections between neurons, and ultimately the neurons themselves that are responsible for memory and learning, as well as executive function. While it is clear that AD creates widespread damage within the brain itself, it is unclear whether the upstream cause of the disease may lie in changes that occur in the blood, ultimately influencing brain health. Support for this hypothesis can be found in the context of normal aging in which blood factors from old individuals drive characteristics of aging. This proposal will directly investigate how manipulating proteins in the blood influences the impact that the risk-conferring APOE-ε4 gene has on Alzheimer’s disease and the extent to which APOE- ε4’s harmful effects can be rescued with more neutral forms of the gene. The results possibly will provide fresh insights into new treatment avenues.ID:A2018213SJuly 1, 2018 to June 30, 2021Alzheimer's DiseaseStandard$300,000
- Florian Sennlaub, MD, PhDFondation Voir et Entendre (Paris, France)
It has recently been shown that patients with sleep apnea syndrome (SAS) suffer more frequently from age-related macular degeneration (AMD), but the reason for the association of both diseases remains obscure. Our preliminary data suggest that the episodes of hypoxia that characterize sleep apnea activate circulating immune cells and lead to longer and stronger detrimental inflammation in the eye in AMD models. Our project to study immune cell activation and detrimental inflammation by hypoxia might help explain the association of sleep apnea with AMD, and also that of other diseases, such as Alzheimer disease, that are associated with SAS and harmful inflammation. Increased awareness of this mechanism will help to diagnose and treat SAS in affected AMD patients, reducing their need for intra-vitreal injections and slowing the macular degeneration in the future.ID:M2018096July 1, 2018 to June 30, 2020Macular DegenerationStandard$160,000
- Sara Gallant, PhDUniversity of Southern California (Los Angeles, CA)
The ability to selectively remember important information and ignore distraction is critical for optimal memory performance, particularly when we experience a stressful or emotionally arousing event that consumes attentional resources. Evidence suggests that the locus coeruleus (LC), the part of our brain thought to instigate these selectivity processes under arousing conditions, degrades in aging and Alzheimer’s disease (AD). Yet little is known about the relationship between the LC and cognitive function in these populations. The goal of this research is thus to address a novel and critical research question: to determine the role of the LC in facilitating memory selectivity and how its role may be altered in aging and AD.ID:A2018449FMentors:Mara Mather, PhDJuly 1, 2018 to June 30, 2020Alzheimer's DiseasePostdoctoral Fellowship$150,000
This grant is made possible in part by support from Alzheimer’s Los Angeles.
- Yingbin Fu, PhDBaylor College of Medicine (Houston, TX)
Age-related macular degeneration (AMD) is a disease that blurs the sharp, central vision you need for everyday activities, such as seeing faces, reading, sewing, and driving. Advanced AMD can be classified into the dry form (gradual breakdown of the light-sensitive cells in the macula) and the wet form (leaky blood vessels growing under the retina). The current treatment for wet AMD is suboptimal, while there is no treatment available for dry AMD. We propose to develop a novel and effective treatment for both the wet and dry forms of AMD by using a protein called AIBP (apolipoprotein A-I binding protein).ID:M2018142July 1, 2018 to June 30, 2020Macular DegenerationStandard$160,000
This grant is made possible by support from The Helen Juanita Reed Award for Macular Degeneration Research.
- Rosario Fernandez-Godino, PhDMassachusetts Eye and Ear Infirmary, Harvard Medical School (Boston, MA)
Age-related macular degeneration (AMD) affects more than 2 million individuals in the US and it will reach 3 million by 2020. Current therapies can improve vision only in some patients with advanced AMD; unfortunately, there is no effective therapy that prevents disease progression in patients with early disease or genetic predisposition. My aim is to create a cell-based model to discover the primary mechanisms activated by the combination of aging and genetic variants in complement genes in patients with early AMD; so that drugs can be designed to stop these mechanisms before they lead to major damage and legal blindness.ID:M2018115July 1, 2018 to June 30, 2020Macular DegenerationStandard$160,000
This grant is made possible by the Ivan Bowen Family Foundation.
- Chi Luu, PhDCentre for Eye Research Australia (East Melbourne, Australia)
The protective properties of high-density lipoprotein (HDL), “good cholesterol”, have been studied extensively in cardiovascular conditions. Chronic inflammation modifies HDL (to dysfunctional HDL) and impairs its positive functional properties such as anti-oxidant and anti-inflammatory actions. Restoring HDL function has been shown to inhibit inflammation and oxidative stress, and in turn, reduces the risk of cardiovascular diseases in humans. Given that age-related macular degeneration (AMD), an eye condition that causes the loss of central vision, and cardiovascular disease share many common risk factors, we hypothesized that HDL functionality has a role in the development and progression of AMD. The overall aim of this research project is to explore the role and therapeutic benefit of HDL in AMD.ID:M2018144Co-principal Investigators:Robyn Guymer, PhD; Gregory Dusting, PhDJuly 1, 2018 to June 30, 2020Macular DegenerationStandard$160,000