Brightfocus Foundation

“A draft of the federal form 990 is distributed to the audit committee for review prior to being submitted to the internal revenue service. The draft federal form 990 is distributed early enough to provide each committee member with a reasonable amount of time for review and submission of questions or comments prior to the filing deadline. The final federal form 990 is distributed to each member of the full board of directors prior to being filed with the internal revenue service. The draft or final federal form 990 may be distributed in person, by regular mail, e-mail, or fax.”

“Brightfocus has all employees, officers, and directors agree to the code of conduct that includes adherence to the conflict of interest and implementation policy. Each board director, officer, and employee is required to complete a conflict of interest disclosure statement annaually. Employees meet annually with the brightfocus' chief compliance officer to review their conflict of interest statements, and give an annual conflict of interest compliance report to the board chair and vice chair. If a conflict is reported, it is then referred to the president/ceo and/or brightfocus' legal counsel and, if appropriate and necessary, then to the board of directors or its appointed committee for further action. The director's and officer's statements are reviewed by the brightfocus legal counsel. If a conflict is reported, it is then referred to the board of directors or its appointed committee for further action. At the time of the brightfocus discussion and decision concerning a conflict of interest, the conflicted party is not present in the meeting.”

“Brightfocus' board of directors has overall authority and responsibility for approving the annual budget which includes salary and benefits for all employees at every level including non-director officers and key employees. All pay adjustments are made on a yearly basis effective april 1st, the beginning of the brightfocus fiscal year. Before approving the compensation of the president/ceo, the board determines the total compensation to be provided by brightfocus to the president/ceo is reasonable in light of the position, responsibility and qualification of the position held including the result of an evaluation of prior performance for brightfocus, if applicable. The president/ceo is evaluated annually by the board of directors through the use of an in-depth goal attainment structure, (developed with advice from board source) that includes a self assessment and a board of directors assessment and evaluation against set goals, outcomes and deliverables. In addition, the board of directors periodically engages an outside consultant to obtain and consider appropriate data, including a salary survey, which includes information compiled from the federal form 990 of other organizations, concerning compensation paid to ceos in like circumstances. In making the determination, the board of directors shall consider total compensation to include the salary and value of all benefits provided by brightfocus to the individual in payment for services. At the time of the brightfocus board discussion and decision concerning the president/ceo's compensation, the president/ceo is not present in the meeting. The board shall set forth the basis for its decisions with respect to compensation in the minutes of the meeting at which the decisions are made, including the conclusions of the evaluation and the basis for determining that the individual's compensation was reasonable in light of the evaluation and comparability data. The president/ceo is charged with the setting of salaries of all other employees in accordance with a compensation structure and budget approved by the board of directors. The president/ceo and human resources review employee compensation and benefits that include key employees, by periodically engaging an outside consultant to conduct compensation and benefit benchmarking studies that include various regional and national non-profit compensation reports and surveys. Compensation deliberations and decisions include the review of self and supervisory evaluations of employee performance compared to set individual and organizational goals.”

“Brightfocus makes its governing documents including its articles of incorporation and bylaws, the federal form 1023, the 501(c)(3) letter of determination from the internal revenue service, conflict of interest policy, audited financial statements and federal form 990 available to the public upon request. In addition, the public also has access to the annual report, audited financial statements, the 501(c)(3) letter of determination from the internal revenue service, and federal form 990 on our website.”

“Brightfocus funds exceptional scientific research worldwide to defeat alzheimer's disease, macular degeneration, and glaucoma and provides expert information on these heartbreaking diseases. Our vision is: a world free from diseases of mind and sight. Collectively, 1 in 16 people over the age of 40 in the u.s. Has one of these diseases. Brightfocus has a proven track record of supporting the most innovative, early-stage research seeking better understanding, treatments, or, ultimately, a cure for these diseases. Since 1973, brightfocus has awarded more than $224 million in research grants to thousands of scientists around the world. Our research funding has led to major contributions to the understanding of these diseases and support for scientists who have received prestigious awards, including two nobel prizes. An indicator of our ability to push new boundaries of knowledge is that brightfocus-supported research was recently found to have had twice the impact on driving future science than work supported by many other organizations. The world-class research identified and supported by brightfocus is on the cutting-edge of the fight to save mind and sight. Our funding acts as a catalyst in early-stage research. The brightfocus research programs are designed to provide initial funding for highly innovative experimental ideas. Due to the structured grant review and approval process, the research impact of brightfocus is very high. Most recipients of brightfocus funding go on to receive future grants from other sources that are 10 times larger than the original brightfocus award. This high return on brightfocus investment speaks to our ability to identify promising research in its earliest stages and spawn future scientific discoveries. It is our firm belief that having the courage to invest in innovative ideas will lead to revolutionary approaches and life-saving breakthroughs. Along with funding cutting-edge research to find cures to some of society's costliest diseases, brightfocus also provides free educational materials and support to hundreds of thousands of patients and families affected by these diseases nationwide. We root these educational materials in the latest research findings. Brightfocus increases public awareness of alzheimer's, macular degeneration, and glaucoma, and communicates with thought leaders and elected officials about the importance of scientific research in these areas. Brightfocus' award-winning public service announcements (psa) have appeared on television, radio, and in print throughout the nation. The impact of alzheimer's. Make a plan today: get your eyes checked and now is the moment to stop alzheimer's disease powerfully seek to raise awareness and early detection, and similar messages have been delivered through donated print psa space in airports and train stations, as well as at pharmacies, and supermarkets and on line. In fiscal year 2020, these psa messages generated $16,266,962 in donated media services and garnered over 960 million impressions. Since 2014, the brightfocus chats have brought together patients and caregivers for free, interactive monthly telephone forums to learn from, and ask questions of, leading researchers and specialists on vision diseases. The chats are archived on our web site, with audio and print transcripts available in a number of accessible formats. We continue to increase our print publications, many in spanish, that provide helpful information to patients and caregivers, and regularly unveil new video and audio resources in conjunction with allies in the medical and scientific communities. Partnering with several high-profile public and private organizations, brightfocus is helping better educate the public on the importance of participation in clinical research as a way to accelerate the path to cures for neurodegenerative diseases. Specifically, brightfocus is a presentation partner for turning point, a documentary on the scientists and clinical trial volu”

“Notable projects include: using the eye to detect dementia; lifestyle effects on risk of alzheimer's; drug discovery; molecular and digital biomarkers; the role of inflammation in disease risk; scientific exchanges; and better use of modern technologies, including mobile technologies and big data, to increase the speed of clinical trials and research progress. Additional information about specific projects is included in schedules f & i. Brightfocus is honored to have supported the early research of two nobel prize winners: dr. Stanley prusiner and dr. Paul greengard, whose work has been instrumental to our current understanding of alzheimer's disease. Brightfocus continues its partnership with the academic journal "molecular neurodegeneration" as the official journal of the brightfocus foundation. The journal publishes technical papers related to neurodegeneration in the three disease areas. To accelerate scientific progress, it is an "open access" journal, and all content is free of charge. This open access ensures maximal reach of journal contents to scientists and care providers worldwide. Molecular neurodegeneration is currently the highest impact open access journal in the neurosciences. In addition to supporting cutting-edge research, alzheimer's disease research provides excellent resources on detecting, treating, and living with the disease. These are available in both print as well as on our website, www.brightfocus.org. Alzheimer's disease is the only cause of death among the top 10 in america without a way to prevent, cure, or even slow its progression. It is an irreversible degeneration of the brain that causes disruptions in memory, cognition, personality, and other functions and inevitably leads to death. An estimated 5.5 million americans have alzheimer's disease, about two-thirds are women.”

“During the fiscal year ending march 31, 2020, mdr awarded $3,500,818 in peer-reviewed grant awards to 19 new research projects, with 3 additional scientific projects that take the total funding to $3,560,818. Details about specific projects are included in schedules f & i. In addition to supporting cutting-edge research, macular degeneration research provides excellent resources on detecting, treating, and living with this disease. These are available in both print as well as on our website, www.brightfocus.org. Age-related macular degeneration is a leading cause of vision loss in the united states. It destroys the macula, the part of the eye that provides sharp, central vision needed for seeing objects clearly. The most common eye condition in people age 60 and older, it can lead to vision loss in one or both eyes, making it difficult to recognize faces, drive a car, or read.”

“During the fiscal year ending march 31, 2020, ngr awarded $3,079,573 in peer-reviewed grant awards for 17 new projects and one other scientific award to make a total of $3,082,073 in funding. Details about specific projects are included in schedules f & i. In addition to supporting cutting-edge research, national glaucoma research provides excellent resources on detecting, treating, and living with the disease. These are available in both print as well as on our website, www.brightfocus.org. Glaucoma is a group of diseases that damage the eye's optic nerve and can result in vision loss and permanent blindness. More than 3 million americans age 40 and older have glaucoma. More than 60 million people in the world have the disease. With early detection and treatment, glaucoma often can be managed to protect eyes from more serious vision loss, but it is estimated that only half of the people living with glaucoma are aware that they have the disease.”

“Recoveries of prior year grants 233,154. Change in present value of grants -290,798.”

“Region: europe (d) purpose of grant: alzheimer's disease research by jinghui luo, phd, entitled: (a20201759s) structure determination of alzheimer and parkinson associated oligomers in lipidic cubic phase. Investigators summary: in diseases such as alzheimer's and parkinson's, toxic protein lumps form holes in them nerve cells. I want to discover how those lumps assemble at atomic resolution. Grant awarded: $100,000, paul scherrer institute, villigen, switzerland. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201759s. Region: europe (d) purpose of grant: alzheimer's disease research by lucia chavez-gutierrez, phd, entitled: (a20201828s) nanobodies stabilizing gamma secretase-app interactions as novel therapeutics for alzheimer's. Investigators summary: the molecular machinery that produces harmful material (amyloid beta) in the brain of people affected with alzheimer's disease (ad) is well known. We have recently shown that this molecular machinery (called gamma-secretase) is fragile and prone to malfunctioning, but fortunately the use of 'stabilizing' molecular bricks can stop its malfunction and prevent the production of toxic, ad-causing material. In this project we will generate novel stabilizing nanobricks (called nanobodies) to stabilize gamma-secretase and thus prevent the production of toxic amyloid beta. The novel nanobody stabilizers could pave the way for ad therapy. Grant awarded: $299,823, vib-ku leuven center for brain & disease research, leuven, belgium. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201828s. Region: europe (d) purpose of grant: alzheimer's disease research by thomas karikari, phd, entitled: (a2020812f) phospho-tau181: a new blood test to predict alzheimer's disease. Investigators summary: presently, there is no simple way to diagnose alzheimer's disease (ad) or to identify individuals likely to develop the disease in the future: current tests require expensive brain imaging or inconvenient puncture of the spine. To address these challenges, we have developed a high-performance blood test that measures a specific disease-related change (called phosphorylation) on a key ad-associated protein called tau. Initial clinical applications have shown that the new test accurately identifies ad patients and at-risk individuals from healthy patients, and provides important insights into memory decline and brain shrinkage (both key processes associated with the disease) one year ahead. In this study, we propose to investigate, in three uniquely large patient cohorts recruited across three continents and closely monitored for up to a decade, if our new blood test can predict with high accuracy who is likely to develop ad several years ahead, to support early treatment, clinical management and recruitment for therapy trials. Grant awarded: $200,000, university of gothenburg, gothenburg, sweeden. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020812f. Region: europe (d) purpose of grant: alzheimer's disease research conference support. Grant awarded: $94,181, the 15th international conference on alzheimer's & parkinson's diseases, barcelona, spain. Region: north america (d) purpose of grant: national glaucoma research by amanda melin, phd, entitled: (g2020047) omics in a naturally occurring animal glaucoma model. Investigators summary: by leveraging access to a large, existing sample of fresh eye tissues, we examine genes expressed, their sequences, and the metabolites that are present in individuals with and without naturally-occurring glaucoma in a closely related animal model. These data are essentially impossible to obtain for humans and provide a direct way to probe the biological functions that are impacted by glaucoma, along with genetic risk factors. These data have large promise to guide genetic screening panels used in diagnosis and prognosis of glaucoma in humans, and to identify molecules in our”

“Region: east asia & pacific (d) purpose of grant: national glaucoma research by kathryn burdon, phd, entitled: (g2020293) genetic studies of exfoliation syndrome and glaucoma in ethiopia. Investigators summary: genetics can play a role in predicting who requires early treatment for blinding forms of glaucoma, however, we do not fully understand all the genetic contributions to this disease. There is a stark lack of data from non-european populations, particularly those from africa, which is a region with one of the highest burdens of glaucoma. What we know about glaucoma genetics in europeans does not always apply to other populations. This study will investigate genetics of glaucoma in ethiopia, expanding our understanding of glaucoma and aiming to make genetic information useful in the diagnosis and management of glaucoma for patients all around the world. Grant awarded: $198,000, university of tasmania, hobart, tasmania, australia. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020293. Region: east asia & pacific (d) purpose of grant: macular degeneration research by weiyong shen, phd, entitled: (m2020032) preventing subretinal fibrosis in wet amd. Investigators summary: neovascular "wet" age-related macular degeneration (amd) is a major cause of blindness in amd. Patients with wet amd are currently treated with drugs to stop abnormal blood vessel leaking and bleeding but they may still lose vision due to the development of scar tissue under the retina which is irreversible once it has become established. This project will develop a therapy for preventing subretinal scarring in eyes with namd. Grant awarded: $180,000, save sight institute, university of sydney, sydney, australia. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020032. Region: europe (d) purpose of grant: macular degeneration research by sabrina carrella, phd, entitled: (m2020184) mir-181a/b modulation as potential therapeutic approach for amd treatment. Investigators summary: aged macular degeneration (amd) is a common cause of blindness worldwide and the loss of vision is due to progressive loss of specific cell type of the eye important in the visual process. Multiple factors, genetic and environmental factors, are involved in the onset and progression of this disease. We have identified two small molecules (called micrornas) that are able to control many fundamental cellular processes and whose inhibition can protect ocular cells from damage and rescue alterations of vision. We propose to test the beneficial effects of the inhibition of these two micrornas in macular degeneration animal models and pave the way for the setup of a novel therapeutic strategy for this complex disease. Grant awarded: $185,000, fondazione telethon, rome, italy. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020184. Region: europe (d) purpose of grant: macular degeneration research by christopher hammond, md, entitled: (m2020277) exploring the role of the gut microbiome in age-related macular degeneration. Investigators summary: age-related macular degeneration (amd) is a common sight-threatening condition that affects the macula, the part of the retina that allows us to read, see fine detail and recognize faces and it is the leading cause of sight loss in people over the age of 50 years in the developed world. Some diets high in vitamins, such as vitamins c and e are thought to reduce the chances of developing severe, sight-threatening amd although the exact role diet plays is not fully understood. Amd is an inflammatory condition and many research studies have found links between the naturally-occurring bacteria, viruses and fungi in our gut (the gut microbiome) and other common inflammatory conditions associated with aging, such as cancer, heart disease and alzheimer's. The gut microbiome can influence and modify the body's immune responses and may be of relevance in amd. The”

“Name of organization or government: university of california, san francisco. (h) purpose of grant: alzheimer's disease research by hyunjun yang, phd, entitled: (a2020039f) fingerprinting in vivo and in vitro prion strains. Investigator's summary: alzheimer's disease (ad) is associated with the misfolding of tau and amyloid-beta proteins. Ad shares important molecular characteristics with classical prp prion diseases, including the induced misfolding of soluble proteins in an autocatalytic manner and the accumulation of insoluble amyloids. Different "conformational strains" of prp give rise to different neurodegenerative diseases. Conformation sensitive dyes are used to rapidly screen and fingerprint these "conformational strains" of prion proteins. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020039f. Name of organization or government: emory university. (h) purpose of grant: alzheimer's disease research by chadwick hales, md, phd, entitled: (a20201057s) systemic signals from skin in aging and alzheimer's disease. Investigator's summary: age is the strongest risk factor for alzheimer's disease (ad) and the wrinkling of our skin. This study will investigate a link between aging and ad-related changes in the skin and the brain. The ultimate goal of the project is to identify new treatment approaches and new markers of aging and ad in the skin, blood and/or spinal fluid. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201057s. Name of organization or government: the national institutes of health. (h) purpose of grant: alzheimer's disease research by sarah hill, phd, entitled: (a20201086f) investigating coordinated local translation and degradation in axons and the role of ftd-related genes. Investigator's summary: similar to how grocery stores maintain a full shelf of milk cartons by continually selling milk and obtaining new cartons, cells must balance the removal of old and synthesis of new materials. In neurons, insufficient removal of materials or defects in synthesis, lead to loss of neuronal function, accumulation of toxic aggregates, and ultimately neuron death, contributing to the pathogenesis of neurodegenerative diseases such as frontotemporal dementia (ftd). In this proposal i will examine how the distinct processes of removal and synthesis are interrelated. I will use imaging to determine their physical and temporal relationship, drugs to block removal and determine the effects on synthesis, and i will use neurons created from human cells to best determine the extent to which these processes occur during ftd. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201086f. Name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by ganesh babulal, phd, entitled: (a20201142s) using naturalistic driving behavior as a digital, neurobehavioral marker to predict those at risk for preclinical and symptomatic alzheimer disease. Investigator's summary: crashes are a leading cause of injury and deaths among older adults, with as many as 19 older adults killed each day, and crashes are higher among persons with alzheimer disease (ad). Since 2015, we tested a new way to continuously collect driving behaviors (distances, speeding, hard breaking, times of day driving, etc.) by plugging a device into people's cars and recording how they drive. This was termed, driving real-world in-vehicle evaluation system (drives). We will use the drives to see if we can sort out those who have early ad from those who do not. We will also look at whether or not other tests of brain abilities, navigation (finding one's way around), physical functioning, and sensory functioning (vision, hearing, smell) can help tell these individuals apart more accurately. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201142s. Name of organization or government: the university of tex”

“Name of organization or government: indiana university. (h) purpose of grant: alzheimer's disease research by juan codocedo, phd, entitled: (a20201166f) role of hk2 in trem2-mediated microglial response in ad. Investigator's summary: alzheimer's disease is a neurodegenerative disorder that induces the activation of the brain immune cells, the microglia. Mutations in a gene expressed only in microglia, trem2, increase the risk of late-onset alzheimer's. However, the molecular mechanism involved in trem2 function are not fully understood. In this study, we want to evaluate if trem2 can induce metabolic changes in the microglia through the regulation of hexokinase 2 an important enzyme of the metabolism of glucose. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201166f. Name of organization or government: michigan state university. (h) purpose of grant: alzheimer's disease research by scott counts, phd, entitled: (a20201187s) noradrenergic regulation of amyloid clearance in ad. Investigator's summary: the contribution of cerebral amyloid (abeta) angiopathy (caa) and cerebrovascular pathology to the progression of alzheimer's disease (ad) has received renewed interest in the field. This proposal expounds upon compelling preliminary data to test that degeneration of the locus coeruleus (lc) and cholinergic basal forebrain (cbf) projection systems contributes to cognitive impairment through their damaging effects on intramural peri-arterial drainage (ipad) of abeta contributing to ad/caa. If successful, this proposal will advance the clinical rationale for targeting lc/cbf-mediated ipad as a disease modifying strategy. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201187s. Name of organization or government: brigham young university. (h) purpose of grant: alzheimer's disease research by justin miller, phd, entitled: (a2020118f) leveraging heterogeneity in alzheimer's disease to assess differences in longitudinal health outcomes. Investigator's summary: millions of americans watch themselves or their loved ones lose their ability to retain memories as they advance through the devastating stages of alzheimer's disease (ad) with little guidance on how quickly the disease will progress. We carefully designed an approach to use machine learning to group individuals with similar health trajectories based on their genetics, clinical tests, and neuroimages, and we will use these subtypes to assess differences in the rate of cognitive decline, the age of disease onset, and the age of death for each proposed subtype using a longitudinal dataset spanning 20 years. We anticipate that identifying ad subtypes will allow future studies to improve diagnoses for patients, identify subtype-specific drug targets, calculate disease trajectories for each subtype, focus clinical trials on specific subtypes, and eventually develop subtype-specific treatment plans. By better understanding differences in ad, we will provide patients and caregivers with more information about the underlying causes of the disease and the projected health outcomes associated with cognitive decline. In a disease with so many unknowns, having clearer health trajectories and diagnoses gives all of us with hope that we might find a cure for at least some patients, and immediately provides patients and caregivers currently dealing with the effects of ad with more information to make informed end-of-life decisions. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020118f. Name of organization or government: beth israel deaconess medical center. (h) purpose of grant: alzheimer's disease research by peter fried, phd, entitled: (a20201288s) evaluating cortical excitability and plasticity as markers of preclinical ad. Investigator's summary: the goal of this study is to develop tests that can detect changes in the activity of the brain at the earliest stage of alzheimer's disease (ad)”

“Name of organization or government: university of pennsylvania. (h) purpose of grant: alzheimer's disease research by sadaf amin, phd, entitled: (a20201312f) the role of cgas-sting signaling in neuroinflammation and alzheimer's disease. Investigator's summary: there is a high level of neuro-inflammation in the brains of alzheimer's patients. These inflammatory factors are secreted by stressed cells and lead to deterioration of other cell types (e.g. Neurons) present in the brain. My proposal intends to study the molecular pathways that govern this inflammatory response inside the brain and target them to limit the neuronal damage that leads to cognitive deficits and memory loss in alzheimer's disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201312f. Name of organization or government: university of southern california. (h) purpose of grant: alzheimer's disease research by lirong yan, phd, entitled: (a20201411s) characterizing dysfunction of cerebral perforating arteries in vcid and ad using ultra-high-field 7 tesla high resolution mri. Investigator's summary: by sharing with the common vascular risk factors, there is an increasing prevalence of alzheimer's disease and vascular cognitive impairment/dementia (vcid) with age. Small vessel disease (svd) induced by the dysfunction of cerebral perforating arteries is one of the frequent vascular pathologies in the aging brain and vcid. The state-of-the-art 7t mri with increased intrinsic signal to noise ratio (snr) allows us to image the cerebral perforating arteries directly. In this study, we will optimize two high-resolution mri techniques at 7t to quantitatively characterize the structure and flow function of cerebral perforating arteries, and study the role of dysfunction of cerebral perforating arteries in the pathogenesis of vcid/ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201411s. Name of organization or government: university of kentucky. (h) purpose of grant: alzheimer's disease research by simone crivelli, phd, entitled: (a20201464f) pharmacological inhibition of ceramide production in mitochondria as a treatment for alzheimer's disease. Investigator's summary: there is still no cure for alzheimer's disease (ad), therefore, a major challenge for researchers in the field is to develop new therapies that prevent or delay onset of this disease. During the ad process brain cells including neurons are under attack by high levels of the lipid ceramide. The consequence of this elevation is that neurons are not able to produce enough energy and are more easily programmed to die. Hence, in this research proposal, we propose to reduce ceramide levels in the brain to protect neurons from dying as a new therapy for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201464f. Name of organization or government: university of california, san francisco. (h) purpose of grant: alzheimer's disease research by claire clelland, phd, md, mphil, entitled: (a20201490f) therapeutic gene editing in c9orf72 frontotemporal dementia (ftd) and amyotrophic lateral sclerosis (als) patient cells. Investigator's summary: frontotemporal dementia (ftd) and amyotrophic lateral sclerosis (als) are two fatal and incurable neurodegenerative diseases linked by a shared genetic cause a heterozygous hexanucleotide (ggggcc) repeat expansion in a single allele of the c9orf72 gene. The goal of this work is to develop novel crispr based therapeutic gene editing technologies and test whether gene editing can reverse the cellular pathology caused by this repeat expansion in patient derived cells. The results of these studies will advance our use of crispr technologies for therapeutic editing in ftd/als, inform our understanding of the regulation of c9orf72 gene, and will be applicable to many other repeat expansion and single gene disorders. For more information, visit the brightfocus website: www.brigh”

“Name of organization or government: mayo clinic jacksonville. (h) purpose of grant: alzheimer's disease research by chia-chen liu, md, entitled: (a20201542s) modulation of peripheral apoe for alzheimer disease therapy. Investigator's summary: having apolipoprotein e4 (apoe4) gene increases a person's risk, whereas having apoe2 is protective for alzheimer's diseases (ad). Our previous study found that apoe4 produced in the liver compromises the vascular heath and impairs brain function (though apoe4 circulating in the bloodstream does not get into brain). Using our unique mouse model in which apoe2 is produced in the liver of apoe4 mice, our studies will for the first time test whether converting harmful apoe4 to protective apoe2 in the liver can restore brain functions. In addition, we will examine whether treating apoe4 mice with apoe2 young blood promotes aging-related memory deficits and reduces ad disease progression. Our findings will provide preclinical evidence for designing future human clinical trials, which may offer individualized treatment strategies based on apoe genotype. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201542s. Name of organization or government: emory university school of medicine. (h) purpose of grant: alzheimer's disease research by lenora higginbotham, md, entitled: (a20201577f) unraveling the biological overlap of alzheimer's disease and dementia with lewy bodies using integrative brain-csf proteomic analysis. Investigator's summary: dementia with lewy bodies (dlb) is a disabling disease that is difficult to diagnose because it often looks similar to alzheimer's disease (ad). Our research aims to uncover key differences between these two disorders by using cutting edge techniques to analyze protein levels in the brain and its surrounding fluid. Unraveling the biological overlap between these two dementias could help make dlb easier to recognize and effectively treat. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201577f. Name of organization or government: mayo clinic jacksonville. (h) purpose of grant: alzheimer's disease research by mark ebbert, phd, entitled: (a2020161s) therapeutic targets and diagnostics in alzheimer's disease. Investigator's summary: many genes are known to be involved in alzheimer's disease (ad), but exactly how they are involved is unclear. We hope to identify dna and rna changes that drive ad development and progression. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020161s. Name of organization or government: university of notre dame. (h) purpose of grant: alzheimer's disease research by john koren, phd, entitled: (a20201621s) twisting tau aggregates by proline isomerization. Investigator's summary: tau aggregation is a major pathogenic factor in alzheimer's disease. Our studies have identified a family of proteins that alter tau aggregation, including one member of this family can disaggregate tau aggregates into smaller non-toxic entities. The goal of this proposal is to elucidate the mechanisms of this disaggregation towards the ultimate goal of designing therapeutic strategies that mimic this activity. These studies will identify the properties and number of members of this protein family that present this activity while simultaneously examining the properties of tau that facilitate toxic aggregation and accumulation. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201621s. Name of organization or government: university of california, irvine. (h) purpose of grant: alzheimer's disease research by christel claes, phd, entitled: (a20201625f) transcriptomic and lipidomic analysis of heterozygous and homozygous trem2 r47h human ipsc-derived microglia in chimeric ad mice. Investigator's summary: alzheimer's disease (ad) is the most common type of dementia that causes problems with memory, thinking and behavior, and so far we don't”

“Name of organization or government: the salk institute for biological studies. (h) purpose of grant: alzheimer's disease research by isabel salas, phd, entitled: (a20201645f) targeting astrocyte factors to prevent synaptic alterations in alzheimer's disease. Investigator's summary: the brain is the center of command of our bodies, controlling our motion, our behavior and our feelings. Its main components, the neurons, process information by making specialized connections (synapses) between them assisted by other important types of cells: the astrocytes. Alzheimer's disease (ad) is associated with alterations in these connections. In this project i aim to restore the correct function of astrocytes, to rescue synaptic defects, in mouse models affected by ad and make a step further to the cure of this devastating disorder. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201645f. Name of organization or government: university of connecticut health center. (h) purpose of grant: alzheimer's disease research by brati das, phd, entitled: (a20201729f) a combo of bace1 inhibitors and mglur pams for alzheimer's therapy. Investigator's summary: amyloid-beta (a-beta) is the main component of amyloid plaques found in the brains of alzheimer's patients. Production of a-beta is nearly stopped by inhibiting bace1 enzyme. Therefore, bace1 inhibitors are used to reduce a-beta production and amyloid deposition. But their use can lead to many side effects that impact learning and storage of memory. Therefore, it is critical to develop new therapeutic strategies. We propose to use bace1 inhibitor drugs in combination with mglur activator drugs. This combination therapy will stop the disease progression and help in memory retention at the same time. We will test our strategy in mice in the current study. Positive results from this study will provide alzheimer's patients a better quality of life. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201729f. Name of organization or government: university of pennsylvania. (h) purpose of grant: alzheimer's disease research by hong xu, phd, entitled: (a20201731f) in vitro amplification of human-derived pathogenic tau conformers using recombinant tau. Investigator's summary: tau aggregates (tauopathy seeds) enriched from the postmortem brains alzheimer's disease (ad) patients exhibit specific biological activity of inducing normal tau into misfolded pathological tau. But the quantity and quality of the tauopathy seeds are very much limited. In the study, we will explore the seeding mechanism of the human tau seeds using in vitro reactions for a better understanding of the pathogenesis of ad and other tauopathies. Moreover, we want to amplify tauopathy seeds in vitro by making use of the self-propagating features of them and promote future studies of tau pathology transmission. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201731f. Name of organization or government: wake forest university. (h) purpose of grant: alzheimer's disease research by shannon macauley, phd, entitled: (a20201775s) katp channel inhibition as a modifier of tau pathology in alzheimer's disease. Investigator's summary: overactive neurons are thought to be a driver of alzheimer's disease (ad) pathology. Therefore, identifying new ways to reduce brain excitability is an important strategy for treating ad. This proposal will explore how targeting the brain's vasculature by repurposing an fda approved drug can dampen overactive neurons and decrease ad pathology. For more information, visit the brightfocus website: www.brightfocus.org/grant/a20201775s. Name of organization or government: the university of north carolina at chapel hill. (h) purpose of grant: alzheimer's disease research by ivana quiroga, phd, entitled: (a2020203f) identifying alzheimer's disease risk genes using 3d chromatin structure and genome editing in ipsc-derived microgli”

“Name of organization or government: washington university. (h) purpose of grant: alzheimer's disease research by maud gratuze, phd, entitled: (a2020257f) impact of microglia and trem2 in tau pathology propagation. Investigator's summary: aggregation of the tau protein in the brain is a hallmark of alzheimer's disease (ad), and the propagation of aggregated tau protein is strongly associated with the degeneration and dementia. In addition, brain immune cells, known as microglia, play a crucial role in ad and the propagation of tau pathology in the brain. Indeed, mutations in trem2, a protein found on microglia, are one of the strongest genetic risk factors for ad. Therefore, we will investigate if decreasing microglia or trem2 levels in the brain can modulate tau propagation. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020257f. Name of organization or government: mayo clinic, jacksonville (h) purpose of grant: alzheimer's disease research by sarah pickles, phd, entitled: (a2020279f) truncated stathmin 2 as a proxy for tdp-43 pathology in frontotemporal dementia and alzheimer's disease. Investigator's summary: currently the medical field lacks reliable biomarkers to identify a subset of frontotemporal dementia and alzheimer's disease (ad) patients with a particular type of pathology in the brain, accumulation of aggregated tar dna binding protein (tdp-43). The production of a new molecule, truncated stathmin 2, arising from tdp-43 aggregation, may be a way to indirectly assess tdp-43 pathology. We propose to develop tools to determine if there is an increased amount of truncated stathmin 2 in spinal fluid from ad and ftd patients compared to controls. These findings have the potential to help separate patients who would benefit from particular therapies in upcoming clinical trials. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020279f. Name of organization or government: university of massachusetts school of medicine. (h) purpose of grant: alzheimer's disease research by christelle anaclet, md, phd, entitled: (a2020321s) role of slow wave sleep in alzheimer's disease behavioral, cellular and molecular manifestations. Investigator's summary: cognitive deficits and sleep disruption are the two major symptoms of alzheimer's disease (ad). Given that sleep is necessary for cognition we will test sleep enhancement as an interventional strategy for reducing the burden of the cognitive deficit in ad, using our new and unique mouse model of sleep enhancement. We will investigate, for the first time, the mechanism by which sleep benefits memory, providing new targets for developing pharmacological and interventional strategies to treat sleep and cognitive symptoms in ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020321. Name of organization or government: joan and sanford i. Weill medical college of cornell university. (h) purpose of grant: alzheimer's disease research by makoto ishii, phd, entitled: (a2020363s) circulating immunometabolic factors in alzheimer's disease. Investigator's summary: irreversible loss of brain cells and brain function may already exist by the time patients start developing memory loss due to alzheimer's disease (ad). Therefore, it is imperative to identify the earliest changes occurring in ad, as they may yield new ways to intervene before irreversible brain damage has occurred. During the very early stages of ad when the memory remains relatively intact, there are significant changes in immune and metabolic function that contribute to ad; however, the underlying cause of these changes remain unclear. The goal of this project is to identify the circulating factors that affect immune and metabolic function early in ad before the memory loss and determine how they are involved in the overall disease process. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020363s. Name of”

“Name of organization or government: university california san francisco. (h) purpose of grant: alzheimer's disease research by elise marsan, md, phd, entitled: (a2020443f) single cell transcriptomics analysis of shared disease mechanisms in ad and ftld. Investigator's summary: alzheimer's disease (ad) and frontotemporal lobar degeneration (ftld) are two highly related neurodegenerative diseases that share several key clinical, genetic and neuropathological features. The goal of my project is to harness the cutting-edge single cell transcriptomic technology to uncover common transcriptomic signatures that contribute to disease progression in ad and ftld. Results from this study will provide important insights to disease mechanisms and an enriched resource for the scientific community. Ultimately, these results will help discover new treatments for these devastating diseases. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020443f. Name of organization or government: harvard medical school. (h) purpose of grant: alzheimer's disease research by michele cavallari, phd, entitled: (a2020653s) assessing the perivascular clearance of brain debris in familial and sporadic alzheimer's disease. Investigator's summary: alzheimer's disease (ad) is the most common cause of dementia in the aging population, yet there is no cure to stop the progression of the disease. We propose to study a protective mechanism that drains outside the brain potentially harmful toxins associated with the development of ad, such as beta-amyloid and tau proteins, and that has been recently characterized in animal models. We will use data from two large international studies of ad to investigate this mechanism in subjects at high risk for developing dementia associated with the disease. In investigating this mechanism for the first time in humans, our study could set the ground for future development and testing of therapeutic approaches to prevent the development of ad dementia. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020653s. Name of organization or government: the jackson laboratory. (h) purpose of grant: alzheimer's disease research by alaina reagan, phd, entitled: (a2020677f) determining mechanisms by which variations in the mthfr gene cause cerebrovascular damage. Investigator's summary: historically, beta-amyloid plaques and tau tangles have been the focus of alzheimer's disease (ad) research. However, there is increasing evidence that brain vascular health is a critical component in the progression of the disease. A variant in the mthfr gene has been linked to both vascular disease and ad in humans, but until now, no animal model represented this risk factor. Here, we have created a novel mouse model to study how mthfr deficiency affects brain vascular health with age. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020677f. Name of organization or government: boston university. (h) purpose of grant: alzheimer's disease research by manveen sethi, phd, entitled: (a2020687f) involvement of the extracellular matrix in the pathophysiology of alzheimer's disease: a glycomics and proteomics study. Investigator's summary: alzheimer's disease (ad) is a leading cause of dementia, involving cognitive decline, loss of independence and behavioral issues. Identifying the biomolecular deregulation associated with ad is crucial to decode the underpinning disease mechanisms, to discover new biomarkers, and to improve treatment strategies. This project will utilize an analytical workflow, allowing the exploration of the structure and biology of proteins and glycans in ad from patient tissue specimens. Outcomes of this project will benefit ad patients by generating the fundamental, previously unattainable, glycobiological knowledge required to improve the diagnosis and treatment of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020”

“Name of organization or government: baylor college of medicine. (h) purpose of grant: alzheimer's disease research by shuo wang, phd, entitled: (a2020845f) the role of lysosome-to-nucleus signaling and regulation in tau pathogenesis. Investigator's summary: accumulation of tau aggregates in alzheimer's disease patient brains influences brain health and cognition. These aggregates are degraded by an intracellular organelle called the lysosome. Tfeb plays a critical role in regulating lysosomal function and its clearance ability. Our proposal investigates how tfeb works with the goal to identify ways to harness the lysosomal function to promote brain health and combat age-associated neurodegenerative diseases. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020845f. Name of organization or government: massachusetts general hospital. (h) purpose of grant: alzheimer's disease research by eunhee kim, phd, entitled: (a2020870f) the impact of the exercise hormone irisin on astrocytes in alzheimer's disease. Investigator's summary: exercise reduces the risk of developing alzheimer's disease (ad) by up to 50 percent and protects against ad by modulating the inflammation which is heavily dependent on brain immune cells: astrocytes. Irisin is a novel exercise-induced hormone that has been identified to possess several beneficial aspects of exercise. This work aims to understand the functional role of the exercise-hormone irisin in ad pathogenesis, and the underlying molecular mechanism of the neuroprotective effects of irisin in ad by regulating astrocytes. The data obtained in this proposal will be used to advance our knowledge of irisin and astrocytes in ad, and ultimately, toward novel therapeutic designs that mimic the beneficial effects of exercise. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020870f. Name of organization or government: brigham and women's hospital. (h) purpose of grant: alzheimer's disease research by peng li, phd, entitled: (a2020886s) circadian regulation, autonomic function, and alzheimer's disease. Investigator's summary: cure for alzheimer's disease (ad) is still lacking. It is important to identify the risk factors for the disease and its multiple impacts on body functions in order to prevent or slow down the progression of the disease and treat related symptoms. Using novel non-invasive assessment of circadian regulation and autonomic function by wearable technology, this project is designed to determine whether changes in these two important physiological functions can predict the development and progression of ad and cognitive decline in the elderly people at early, preclinical stages. This project may potentially provide new intervention targets in future clinical studies of ad, and can lay the groundwork for the design of novel unobtrusive, cost-efficient tools for long-term monitoring of cognitive impairment or risk for ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020886s. Name of organization or government: university of california, san francisco. (h) purpose of grant: alzheimer's disease research by lydia le page, phd, entitled: (a2020928f) imaging brain ketone metabolism in alzheimer's disease. Investigator's summary: the ketogenic diet is thought to provide an alternative fuel for the struggling brain in alzheimer's disease (ad) but is this fuel actually being used to make energy? Currently we have no way of knowing. We will develop a new way of imaging the brain to see if it is using the ketones as fuel, and use the method to discover new insights into brain ketone metabolism in a mouse model of ad. For more information, visit the brightfocus website: www.brightfocus.org/grant/a2020928f. Name of organization or government: mayo clinic, jacksonville. (h) purpose of grant: alzheimer's disease research by entitled: (ca2017563) molecular neurodegeneration journal. Investigator's summary: we par”

“Name of organization or government: university of pennsylvania. (h) purpose of grant: alzheimer's disease research by entitled: travel sponsorship for attendees at international genomics of alzheimer's project meeting. Name of organization or government: national institutes of health/ national institute of neurological disorders and stroke. (h) purpose of grant: alzheimer's disease research by amir kashani, md, phd, entitled: (ca2020004) optical coherence tomography angiography based assessment of retinal capillary density as a biomarker of vascular cognitive impairment and dementia. Investigator's summary: vascular contributions to cognitive impairment and dementia (vcid) arise from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior. Vcid often occurs in and contributes to alzheimer's disease dementia. The damage in the small blood vessels is very difficult to detect with conventional testing or brain imaging methods like magnetic resonance imaging (mri). The goal of dr. Kashani's research is to develop new methods using the eye to detect the onset, progression and severity of vcid. Name of organization or government: boston university school of medicine. (h) purpose of grant: alzheimer's disease research by benjamin wolozin, md, phd entitled: (ca2020002) development of synthetic gene feedback circuits to prevent tau aggregation. Investigator's summary: the failure of current therapeutic approaches to alzheimer's disease (ad) highlights the need for new, innovative technologies to address ad. This proposal uses a radically novel approach termed "synthetic biology", which utilizes circuit designs inspired by electrical engineering to create novel regulatory circuits that drive genes with therapeutic promise. In this proposal, we will apply these novel genetic engineering approaches to create synthetic gene networks that are able to reduce or even reverse the progression of ad. Name of organization or government: university of denver. (h) purpose of grant: alzheimer's disease research by ann charlotte granholm-bentley, phd, entitled: (ca2018010) international brain bank for down syndrome-related alzheimer's disease. Investigator's summary: the focus of this special project is to develop a strong collaborate network between six different research groups focused on providing much-needed information about the down syndrome population, of which as many as 80 percent have alzheimer's pathology by the time they are in their 50s and 60s. Although there are many centers and researchers that focus on alzheimer's in the general population, few of them focus on people with down syndrome. The information generated by our project will be of great help to those with down syndrome and those with alzheimer's disease. Name of organization or government: the milken institute. (h) purpose of grant: project support for study on "lowering the price and risk of dementia: policy recommendations to improve brain health and reduce disparities." name of organization or government: the milken institute. (h) purpose of grant: project support for study on neurotechnology that includes identifying areas for future investment in research. Name of organization or government: university of rochester medical center. (h) purpose of grant: national glaucoma research by richard libby, phd, entitled: (g2020095) neurotoxic cytokine signaling in glaucoma. Investigator's summary: this work explores the importance of extrinsic signalling in glaucomatous neurodegeneration. It builds on the work of many groups who have proposed that after an ocular hypertensive injury, glial cells (cells that support retinal neurons) transition from being helpful to retinal ganglion cells to being toxic. Specifically, we propose to test the importance of three molecules thought to turn glial cells neurotoxic after a glaucomatous injury. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020095.”

“Name of organization or government: university of iowa. (h) purpose of grant: national glaucoma research by john fingert, md, phd, entitled: (g2020119) apbb2 gene regulation and risk for glaucoma. Investigator's summary: our research has identified a new gene (apbb2) that is the first risk factor for glaucoma that is unique to african american populations and may explain in part why they are at much higher risk for glaucoma that other groups. Our preliminary data suggests that apbb2 promotes risk for glaucoma by increasing production of apbb2 protein in the retina and in turn increasing deposition of toxic beta-amyloid there too. The current proposal seeks to understand what dna sequences are responsible for controlling apbb2 gene activity and thus the production of beta amyloid in the retina and risk for glaucoma. We are especially excited about the overlap between what we are learning about glaucoma biology with our research and what is known about alzheimers disease and how our experiments may benefit both areas of investigation. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020119. Name of organization or government: oregon health and science university. (h) purpose of grant: national glaucoma research by yali jia, phd, entitled: (g2020168) cellular-resolution visible-light oct for early identification of glaucomatous neurodegeneration. Investigator's summary: glaucoma is a leading cause of irreversible vision loss and blindness. Currently, diagnosis and scientific understanding of glaucoma is limited by the inability of medical instruments to image the eye in sufficient detail to detect the earliest changes that presage the disease. By improving current state-of-the-art ocular imaging systems using optical tools originally developed for astronomy, we will enhance image quality so that even individual eye cells can be clearly seen. Using the instrument we develop, we will perform experiments on rodent models in order to discover new and improved indicators of glaucoma progression and help understand the nature of the disease. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020168. Name of organization or government: the schepens eye research institute. (h) purpose of grant: national glaucoma research by petr baranov, md, phd, entitled: (g2020231) targeted maturation of stem cell-derived rgcs. Investigator's summary: retinal ganglion cells (rgcs) are highly specialized neurons, which connect the photosensitive part of the eye with the appropriate targets in the brain. While rgcs exhibit limited plasticity and can form new cell-to-cell connections throughout our life, their number is fixed and no new cells arise postnatally. Thus, any stress factors leading to ganglion cell death, such as high intraocular pressure in glaucoma, trauma or drug toxicity, result in irreversible vision loss. In our pilot studies we have demonstrated that mouse retinal ganglion cells may be produced from renewable cell source - pluripotent stem cells and successfully delivered into the mouse eye. In this proposal we aim to improve the donor, stem cell-derived rgcs more mature and developmentally closer to the "real" rgcs. That should significantly increase the transplantation success, leading to potential therapy development. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020231. Name of organization or government: the jackson laboratory. (h) purpose of grant: national glaucoma research by gareth howell, phd, entitled: (g2020254) deciphering the role of the cdkn2b-as region in glaucoma. Investigator's summary: human genetic studies show glaucoma is caused by a combination of genetic risk factors. However, few specific changes have been determined. This is severely hampering our ability to identify those at risk of developing glaucoma and developing new treatments. In this study we aim to determine the specific genetic element in a genomic region t”

“Name of organization or government: university of pittsburgh. (h) purpose of grant: national glaucoma research by jeffrey gross, phd, entitled: (g2020277) identification of novel genes and pathways that protect rgcs from injury-induced death. Investigator's summary: during glaucoma, retinal ganglion cell (rgc) axons are damaged and this causes the rgcs to die, ultimately resulting in the irreversible loss of visual function. Currently, there are no fda-approved drugs or therapies to protect rgcs from death in glaucoma. Experiments in this proposal utilize the zebrafish as a model system, leveraging its unique biology where rgcs do not die when their axons are damaged, even in extreme cases when the optic nerve is completely severed. By understanding how zebrafish rgcs survive after axonal damage we will uncover novel modes of neuroprotection that could ultimately be translated into new targets for neuroprotection to preserve rgcs in glaucoma patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020277. Name of organization or government: emory university. (h) purpose of grant: national glaucoma research by jeffrey boatright, phd, entitled: (g2020286) nicotinamide riboside as treatment in models of retinal ganglion cell damage. Investigator's summary: mitochondria are the energy factories of cells. The mitochondria of retinal ganglion cells lose function with age, probably due to age-related loss of nicotinamide adenine dinucleotide (nad+), an enzyme cofactor needed for energy production. The cells thus become more susceptible to damage from, for instance, elevated pressure in the eye, a common risk factor for glaucoma. We propose to test whether systemic delivery of the nad+ precursor nicotinamide riboside, a dietary supplement, increases retinal nad+ and protects retinal ganglion cells in mouse models of glaucoma. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020286. Name of organization or government: johns hopkins university. (h) purpose of grant: national glaucoma research by jeff mumm, phd, entitled: (g2020315) novel zebrafish models enabling studies of rgc regeneration. Investigator's summary: to restore visual function to glaucoma patients, therapies are needed that can replace the specific cell types in the eye that are lost, retinal ganglion cells (rgcs). Although humans do not normally regenerate lost rgcs, our eyes do retain a capacity to produce new neurons, suggesting an untapped potential for rgc regeneration. Unlike us, zebrafish have a natural ability to replace lost cells in the retina, including rgcs. By studying how zebrafish are able to naturally regenerate lost rgcs, we hope to 1) identify genes and pathways that are important for stimulating the eyes ability to repair itself and 2) apply this knowledge toward the development of transformative regenerative therapies for glaucoma patients. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020315. Name of organization or government: university of utah. (h) purpose of grant: national glaucoma research by karen curtin, phd, entitled: (g2020317) prognostic factors and predictive markers of progression to exfoliation glaucoma in exfoliation syndrome. Investigator's summary: in patients with exfoliation syndrome, which is marked by abnormal threadlike white fibers in the front of the eye that accumulate over time, can we correctly predict who will go on to develop a buildup of pressure in one or both eyes known as glaucoma, a leading cause of blindness worldwide? We believe the answer is 'yes.' from researching thousands of medical records of exfoliation patients to find the clinical conditions and personal characteristics that correlate with changes in the eyes of our exfoliation patients over time, we will help doctors who care for these patients prevent or delay loss of vision from glaucoma through earlier medical treatment. For more information, visit the br”

“Name of organization or government: indiana university. (h) purpose of grant: national glaucoma research by jason meyer, phd, entitled: (g2020369) astrocyte effects on rgcs in a stem cell model of glaucoma. Investigator's summary: astrocytes are known to play vital roles in the maintenance of retinal ganglion cells, with these interactions adversely affected in glaucoma. In particular, as is common across a number of neurodegenerative diseases, the mitochondria of these cells are damaged, presumably leading to the disease phenotypes. The use of human pluripotent stem cells allows for the precise modeling of these interactions in a dish, providing the spatial and temporal resolution to closely examine how mitochondrial function is changed in these cells as a result of glaucoma, as well as how these changes in mitochondria alter the health and function of the cells as a whole. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020369. Name of organization or government: university of tennessee health science center. (h) purpose of grant: national glaucoma research by siamak yousefi, phd, entitled: (g2020374) impact of glaucoma on retinal ganglion cell subtypes. Investigator's summary: glaucoma is the second leading cause of blindness worldwide. It affects over 90 million people and its incidence is predicted to rise 2-fold over the next two decades. Glaucoma-induced vision loss and blindness result from the slow degeneration and death of retinal ganglion cells (rgcs). In human, the large population of rgcs can be subdivided into at least 30 subtypes. The susceptibility of rgc subtypes to glaucoma-induced cell degeneration differs significantly. But it has been surprisingly difficult to identifying both rgc subtypes and their susceptibility to glaucoma. For the past three years we have been developing single-cell technologies to study both rgc type and the early signature of glaucoma-associated cellular stress. We will develop artificial intelligence (ai) approaches to identify rgc subtypes that are more susceptible to glaucoma-induced insult. Our results could advance our understanding of the genetic bases for glaucoma-induced rgc cell death and possible therapeutic interventions. For more information, visit the brightfocus website: www.brightfocus.org/grant/g2020374. Name of organization or government: university of massachusetts school of medicine. (h) purpose of grant: macular degeneration research by claudio punzo, phd, entitled: (m2020016) elucidating how smoking contributes to amd. Investigator's summary: age-related macular degeneration (amd) is the leading cause for blindness among elderly of the industrialized world. Among the non-genetic risk factors smoking confers the highest risk for progression to the advanced stages of geographic atrophy (ga) and exudative amd; however, how smoking contributes to amd remains elusive. Here we propose that smoking causes advanced amd pathologies by depletion of the second most abundant serum protein. Loss of this serum protein in humans causes emphysema, a condition that has been linked to increased risk for advanced amd, while we found that loss of this serum protein in mice, causes besides lung problems, late stage amd pathologies. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020016. Name of organization or government: university of virginia. (h) purpose of grant: macular degeneration research by bradley gelfand, phd, entitled: (m2020114) pathophysiology of choroidal hemodynamics in amd. Investigator's summary: the choroid is the blood vessel network that nourishes the retina, and is a site of age-related macular degeneration (amd). Recent studies suggest that choroidal blood flow is reduced in amd, and that loss of choroidal blood flow may be an important factor in the initiation and progression of the disease. In this proposal, we will use donor eyes and cutting edge computer modeling and to cellular models to und”

“Name of organization or government: the city college of cuny. (h) purpose of grant: macular degeneration research by mark emerson, phd, entitled: (m2020157) a screen for cone-promoting factors that can be used to replace cones lost in amd. Investigator's summary: cone photoreceptors are the critical light sensing sensory cells that are lost in age-related macular degeneration (amd). One promising therapeutic strategy would be to promote the formation of new cone photoreceptors within the retina to replace those lost to disease. This project will use high-resolution molecular techniques to identify the genes normally found in forming cone photoreceptors that are sufficient to turn other retinal cells into cones. The identification of such genes will be provide the foundation to develop new cone replacement therapies for amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020157. Name of organization or government: tulane university. (h) purpose of grant: macular degeneration research by shusheng wang, phd, entitled: (m2020166) a crispr-based inducible system for vegf repression for amd. Investigator's summary: current anti-vegf medicines for wet age-related macular degeneration (amd) require multiple injections per year and is not satisfactory for wet amd patients. We aim to establish a novel inducible system for vegf repression for wet amd. This system combines potency, reversibility and safety, and can be used to treat amd with just one ocular injection. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020166. Name of organization or government: duke university. (h) purpose of grant: macular degeneration research by priyatham mettu, md, entitled: (m2020168) regulation of macrophage-mediated neovascular remodeling in neovascular amd. Investigator's summary: wet (or neovascular) age-related macular degeneration (amd), which develops when an abnormal blood vessel grows under the retina, is the leading cause of blindness in the elderly. While there are approved treatmentsshots of medicines into the eye to stabilize the abnormal blood vesselat least 40% of patients have more severe disease that remains active and causes worsening vision in spite of treatment. We propose that the severe form of wet amd is caused by inflammatory cells called macrophages and have identified a potential novel molecular target that controls the activity of these inflammatory cells. The purpose of this project is to better understand this molecular target and determine whether medicines that block this target could be effective novel treatments for patients with wet amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020168. Name of organization or government: wilmer eye institute, johns hopkins university. (h) purpose of grant: macular degeneration research by malia edwards, phd, entitled: (m2020174) the impact of subretinal glial membranes in geographic atrophy. Investigator's summary: this proposal will take a novel approach to studying the pathology of geographic atrophy by investigating the role of glial cells. These cells, traditionally considered only support cells, are altered in geographic atrophy and create a membrane-like structure. The proposed studies will investigate how changes to these cells may influence disease progression and the effectiveness of treatments. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020174. Name of organization or government: oklahoma medical research foundation. (h) purpose of grant: macular degeneration research by willard freeman, phd, entitled: (m2020207) inducible cell-specific mouse models for paired epigenetic and transcriptomic studies of microglia and muller glia in age-related macular degeneration. Investigator's summary: aging is the major risk factor for age-related macular degeneration (amd) but how aging, along with sex, lead to the development of the disease is not u”

“Name of organization or government: university of washington. (h) purpose of grant: macular degeneration research by jennifer chao, md, phd, entitled: (m2020217) rpe modeling on a perfusable microvessel network. Investigator's summary: in order to identify novel targeted therapeutics for the treatment of age-related macular degeneration (amd) and other rpe-related diseases, there is a critical need to develop physiologically relevant models for understanding disease pathology. Current approaches to modeling rpe-related diseases utilize conventional two-dimensional systems that do not accurately recapitulate normal rpe physiology or disease states, in part, because they do not include the underlying circulation or choroidal vasculature. Recent studies in amd increasingly point toward the importance of the choroid in disease development and progression. The goal of this proposal is to develop and characterize a 3d flow-directed rpe-choroid scaffold system that can be used as a platform to study the essential elements of rpe-related diseases, such as extracellular matrix remodeling, drusen deposition, vascular flow effects on choroidal endothelial cells, and vascular permeability to macromolecules and metabolites. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020217. Name of organization or government: the research foundation for suny on behalf of university at buffalo. (h) purpose of grant: macular degeneration research by amy millen, phd, entitled: (m2020227) interplay of diet and the gut microbiome in age-related macular degeneration. Investigator's summary: the proposed research to study the gut microbiome as a modifiable risk factor for age-related macular degeneration (amd) is relevant to public health because amd is the leading cause of vision loss in the u.s. Using data from the carotenoids in age-related eye disease study 2 (careds2) of postmenopausal women, we propose to conduct one of the first large epidemiologic studies to examine associations between the composition and diversity of the gut microbiome and the prevalence and stage of amd (no amd, intermediate amd, and advanced/vision-threatening amd). Evidence of a protective association between certain profiles of the gut microbiome content and amd could lead, in the long-term, to easily implemented, low-cost interventions to modify the gut microbiome with diet, or highlight potential metabolic pathways for intervention, to prevent amd. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020227. Name of organization or government: university of california davis school of medicine. (h) purpose of grant: macular degeneration research by glenn yiu, md, phd, entitled: (m2020247) crispr-based genome editing for treatment of neovascular amd in the nonhuman primate. Investigator's summary: age-related macular degeneration (amd) is a leading cause of blindness in the elderly, but current treatments for the "wet" form of amd rely on frequent drug injections into the eye that are expensive and a burden for patients. This research proposal will address this healthcare crisis by developing a potential cure for wet amd using a powerful gene-editing technology called "crispr." this innovative gene-editing system can permanently change the genes that cause wet amd, and can hopefully be used someday to save the vision of our aging population. For more information, visit the brightfocus website: www.brightfocus.org/grant/m2020247. Name of organization or government: the national institutes of health/national eye institute. (h) purpose of grant: macular degeneration research by kapil bharti, phd, entitled: (m2020258) discovering mechanisms of rpe/choroid degeneration in amd using 3d bioprinted eye tissue. Investigator's summary: the role of retinal pigment epithelial cells and retinal blood vessels in the progression of age-related macular degeneration, a disease that leads to progressive vision loss with age, are not fu”