Brightfocus Foundation

“A draft of the federal form 990 shall be distributed to the audit committee for review prior to being submitted to the internal revenue service. The draft federal form 990 shall be 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 shall be distributed to each board member prior to being filed with the internal revenue service. The draft and final 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 annually to complete a conflict of interest disclosure statement. Employees meet annually with the brightfocus chief compliance officer to review their conflict of interest statements, and gives 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 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.”

“The brightfocus foundation (brightfocus) board of directors has overall authority and responsibility for approving the annual budget which includes compensation for all employees at every level including non-director officers. 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 ceo, the board of directors determines the total compensation to be provided by brightfocus to the 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 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 ceo's compensation, the ceo is not present in the meeting. The board of directors 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 ceo is charged with the setting of salaries of all other employees in accordance with the budget approved by the board of directors. The ceo and human resources review employee compensation and benefits, that includes 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, 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, the federal form 1023, audited financial statements, the 501(c)(3) letter of determination from the internal revenue service, and federal form 990 on the brightfocus website.”

“Brightfocus foundation seeks to save mind and sight by funding innovative research worldwide and by promoting better health through education. We focus our efforts on three incurable diseases affecting mind and sight: alzheimer's disease, macular degeneration, and glaucoma. Collectively, 1 in 16 people over the age of 40 in the u.s. Alone 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 $150 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 to the awarding of two nobel prizes. Brightfocus-supported findings are consistently cited by other scientists at twice the frequency as other research findings. 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 one thousand percent 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. Indisputably, the world-class research identified and supported by brightfocus is more than promising: it is making a real contribution to revolutionary science in the fight to save mind and sight. 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 base these educational materials off of 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. Both 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. In fiscal year 2015, these psa messages generated $11,473,608 in donated media services and garnered 1.3 billion impressions. Starting in february 2014, we launched brightfocus chats, a free, interactive monthly telephone forum that brings together patients and caregivers 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. We have expanded our written content of key research findings, promoting and sharing this information through our web site and social media platforms. Capitalizing on emerging use of data visualization, our brightfocus "snapshot" series graphically communicates information on alzheimer's, macular degeneration, and glaucoma. Through our social media and web resources, we conduct contests and promotions to increase awareness”

“Recoveries of prior year grants 446,630. Change in present value of grants 14,144.”

“Region: north america (d) purpose of grant: alzheimer's disease research by donald redelmeier, md, frcpc, mshsr, facp entitled: (a2015284s) statins and long-term risk of dementia after concussion. Investigator's summary: concussion affects about one million north americans each year, disproportionately involving people over age 65 years (seniors). Alzheimer's disease is a potential long-term consequence of concussion in seniors, and strategies to prevent such subsequent disorders are a priority for research. Recent studies suggest that statins (cholesterol lowering medications) have protective effects that might prevent short-term complications of concussion by reducing brain swelling, preserving blood flow, lessening inflammation, and preventing cell death. We propose a computerized study linking multiple healthcare databases (anticipated sample size = 300,000, median follow-up duration = 10 years) to test whether statin treatment might decrease the risk of subsequent dementia in seniors following a concussion. Grant awarded: $159,888, sunnybrooke research institute, toronto, canada. Region: north america (d) purpose of grant: alzheimer's disease research by jerome robert, phd entitled: (a2015324f) development of a novel tissue engineered model of the cerebrovasculature. Investigator's summary: with every heartbeat, one quarter of all the blood in the body flows through the brain, and this activity is essential to keep neurons in the brain healthy throughout life. Although scientists realize that understanding how to keep blood vessels in the brain healthy may offer new ways to treat brain disorders including alzheimer's disease (ad), a big challenge is that there are not many methods to study the brain's blood vessels outside of an animal model, and animals models may not always mimic the human condition closely enough to provide answers that help to develop effective treatments for dementia. We have made considerable progress in being able to grow functional three dimensional human-derived blood vessels in the test tube using "tissue engineering" technology, and request support to help adapt this technology to make brain blood vessels that mimic those in the human brain. Our technologies will be used to rapidly test several questions about how these vessels become damaged in ad and how to prevent or repair this damage. Grant awarded: $100,000, university of british columbia, vancouver, canada. Region: north america (d) purpose of grant: alzheimer's disease research by francis hane, phd entitled: (a2015344f) development of hyper-polarized 129xe gas magnetic resonance imaging based alzheimer's disease early detection molecular probe. Investigator's summary: alzheimer's disease is believed to be caused by a protein structure called amyloid oligomers. These amyloid oligomers occur on the surface of brain cells in advance of alzheimer's symptoms. I propose to create a molecule which will bind to these oligomers and can be imaged using magnetic resonance imaging. This will create a method to provide up to 10 years advance notice of alzheimer's disease. This early detection will allow preventative therapies to be started earlier where they are more likely to be effective. Grant awarded: $100,000, lakehead university, thunder bay, canada. Region: europe (d) purpose of grant: alzheimer's disease research by matthew campbell, phd entitled: (a2015548s) novel amyloid-beta clearance mechanisms at the blood-brain barrier. Investigator's summary: alzheimer's disease (ad) is characterized by accumulation of a small peptide, amyloid-beta, in the brain and impaired clearance of amyloid-beta in sporadic ad patient brains appears to be a major factor in this build-up. Positioned along the cerebral blood vessels, the blood-brain barrier (bbb) functions as a tightly regulated site of macromolecule exchange between the brain tissue and circulation and previous work has identified transcellular receptors of amyloid-beta at the bbb. We have shown t”

“Region: east asia & pacific (d) purpose of grant: alzheimer's disease research by veer bala gupta, phd entitled: (a2015641f) developing a blood-based biomarker panel for alzheimer's disease. Investigator's summary: while much progress has been made over understanding alzheimer's disease (ad) pathology and using neuroprotective strategies and some effort spent on brain imaging changes in ad we still lag far behind in developing reliable, sensitive, non-invasive and cost-effective diagnostic biomarkers which can be used before and during the course of a therapeutic intervention. There is substantial evidence to indicate that early stages of alzheimer's disease coincide with specific protein changes in peripheral body fluids particularly blood and these changes subsequently also reflect aggravation of ad pathology during its time-course. Age related protein changes pose a major hurdle to identify and differentiate the specific ad biomarkers due to high prevalence of the disease in aged populations. We propose that investigating familial form of ad will be an innovative approach to identify and develop reliable blood-based biomarkers for this disease. Grant awarded: $100,000, edith cowan university, jondaloop, australia. Region: north america (d) purpose of grant: national glaucoma research by judith west-mays, phd entitled: (g2015052) genes involved in anterior segment dysgenesis and glaucoma. Investigator's summary: glaucoma is an eye disease, which is a leading cause of visual disability in the united states (more than 2.7 million cases of the open-angle form) and throughout the world (more than 60 million cases of the open-angle form). Developmental ocular disorders in humans can lead to glaucoma. The goals of this proposal are to determine the genes involved in these developmental disorders, as well as create animal models of glaucoma to further understand the pathophysiology of the disease and how we may cure it. Grant awarded: $100,000, mcmaster university, hamilton, canada. Region: europe (d) purpose of grant: national glaucoma research by caroline klaver, md, phd entitled: (g2015084) genetics in glaucoma patients of african descent, the giga study. Investigator's summary: glaucoma is a leading cause of blindness in the world, and is particularly frequent among persons of african descent. Genetic studies are currently investigating the causes for this disease, but have thus far mostly shed light on the disease in persons of european descent. With this proposal, we aim to find the genetic causes for glaucoma in african populations. This will help us understand why glaucoma is so frequent in africa, provide us with knowledge on the causes of glaucoma, and help create means to cure and prevent this disease. Grant awarded: $100,000, erasmus medical center, rotterdam, netherlands. Region: east asia & pacific (d) purpose of grant: national glaucoma research by vicki chrysostomou, phd entitled: (g2015125) harnessing exercise to protect the optic nerve. Investigator's summary: exercise is a positive lifestyle choice that reduces the risk for a wide range of diseases and conditions. Yet, the role of exercise in eye health and eye disease is largely unknown. In this project we will investigate how exercise may benefit the optic nerve, the structure joining the eye to the brain, which is primarily affected in the eye disease glaucoma. The information gained from this work will contribute to the development of new approaches for preventing or delaying optic nerve damage and subsequent vision loss in glaucoma. Grant awarded: $99,705, centre for eye research australia, the university of melbourne, e. Melbourne, australia.”

“Region: europe (d) purpose of grant: national glaucoma research by darryl overby, phd entitled: (g2015145) towards a unifying theory for unconventional outflow in mice. Investigator's summary: glaucoma is a leading cause of irreversible blindness, where the open-angle form affects approximately 60 million people worldwide. All treatments for glaucoma focus on lowering pressure within the eye to stop further vision loss, but the biological mechanisms controlling eye pressure are not well understood. In order to develop better drug therapies that more successfully lower eye pressure, we must conduct studies in animals, and mice are often used for glaucoma research. However, there are unanswered questions about whether eye pressure in mice is controlled by the same mechanisms that control eye pressure in humans, neither of which are fully understood. This project will determine whether mice mimic the regulatory mechanisms of eye pressure as occur in humans, so to establish whether studies in mice are valid for identifying new drugs to lower eye pressure in humans grant awarded: $100,000, imperial college london, london, uk. Region: europe (d) purpose of grant: macular degeneration disease research by diana pauly, phd entitled: (m2015186) complement-based immunotherapy for macular degeneration. Investigator's summary: genetic studies showed, that people who are lacking in two proteins (called cfhr1 and cfhr3) of the immune system, are at a decreased risk of developing age-related macular degeneration (amd), the most common cause for vision impairment in the aging population of industrial countries. The immunological function of these proteins is not known. We will shed light on the mechanism of cfhr1 and cfhr3 action in the human body. For this research, we will generate an array of protein tools, designed such that some of them will eventually be developed into novel therapeutics for the inhibition of overactive inflammation in the human eye during amd pathology. Grant awarded: $160,000, universitatsklinikum regensburg (university hospital regensburg), regensburg, germany. Region: europe (d) purpose of grant: macular degeneration disease research by ivan conte, phd entitled: (m2015317) mir-211 in rpe homeostasis and disease. Investigator's summary: age-related macular degeneration (amd) is a major public health problem with devastating effect upon patients and composes a significant socio-economic burden world-wide. Amd affects 30% of individuals aged 70 years and older and its prevalence will rise as life expectancy increases due to changing demographics. In the past few years, significant progress was made on the recognition of the genetic and environmental risk factors that predispose and elicit amd. However, treatment options remain limited because the pathogenetic molecular mechanism of amd are incompletely defined. Recently, some small fragments of the human genome, termed micrornas, have been identified and found to have a fundamental role in many biological processes, both in physiological and in pathological conditions. The goal of this project is the study of the possible role of a microrna, named mir-211, in rpe physiology, survival, homeostasis both as causative agents and as therapeutic agents. Grant awarded: $160,000, fondazione telethon, rome, italy. Region: europe (d) purpose of grant: macular degeneration disease research by stefanie hauck, phd entitled: (m2015370) uncovering novel molecular pathomechanisms in amd by identification of risk snp binding proteins. Investigator's summary: recent advancements in whole genome sequencing have uncovered many genetic variations, so called single nucleotide polymorphisms that correlate with an increased risk to develop age-related macular degeneration during life. Our unique approach aims to discover the biological mechanisms that are affected by these genomic variations, by enrichment and identification of specific proteins and protein complexes which directly bind to the”

“Name of organization or government: baylor college of medicine. (h) purpose of grant: alzheimer's disease research by stacy grunke, phd entitled: (a2015016f) deconstructing entorhinal degeneration and repair in ad. Investigator's summary: these studies will address why layer ii of the entorhinal cortex is severely affected early in the progression of alzheimer's disease. Following loss of entorhinal neurons, we will determine the mechanisms for repair of the circuitry that facilitates functional recovery of memory processing. Name of organization or government: the trustees of columbia university in the city of new york. (h) purpose of grant: alzheimer's disease research by ulrich hengst, phd entitled: (a2015093s) long-range retrograde stress signaling in ad. Investigator's summary: during the development of alzheimer's disease, pathological changes spread between brain regions along the connections of nerve cells called axons. Here we are studying the question what precisely is happening within an axon that connects to a diseased area of the brain and how the neurodegenerative signal is transmitted back to the neuron. The results of our study will allow us to determine whether one can potentially stop this axon-to-neuron transmission of neurodegeneration, thereby stopping the spread of pathology in the brain and preventing to cognitive decline in ad. Name of organization or government: max planck florida institute for neuroscience. (h) purpose of grant: alzheimer's disease research by ryohei yasuda, phd entitled: (a2015251s) the role of centaurin-alpha 1 in alzheimer's disease pathology. Investigator's summary: it is thought that alzheimer's disease is caused by accumulation of beta-amyloid. We recently identified that a signaling protein called centaurin-alpha 1 (centa1) causes beta-amyloid induced dysfunction of neurons and thus potentially contributes to brain dysfunction in alzheimer's disease. In this project, we will further study the potential roles of centa1 in alzheimer's disease using newly developed centa1 knockout mice in combination with the model mice for alzheimer's disease. We hope that this will lead to new therapeutics targeting centa1. Name of organization or government: boston university. (h) purpose of grant: alzheimer's disease research by benjamin wolozin, md, phd entitled: (a2015256s) targeting stress granule biology in alzheimer's disease. Investigator's summary: the function of rna is to help translate the genetic "blueprint" of dna information into actual proteins that execute the majority of functions in a cell. Rna binding proteins (rbps) regulate the conversion of messenger rna to protein through formation of complexes called rna granules. Chemical stresses induce formation of a particular type of complex termed the stress granules (sg). Our preliminary data showed that the neurofibrillary tangles that accumulate in alzheimer's disease (ad) are associated with sgs. In previous work using brightfocus funds, we made the startling finding that tau protein is actually required for sg responses, which means that the pathological changes driving ad are intimately connected to the sg response. We also showed that sg formation stabilizes tau protein, stimulates tau misfolding, and stimulates formation of the insoluble tau that forms the pathology of ad. Equally importantly, we showed that removing a sg protein (tia-1) actually prevents the misfolding of tau associated with ad. This suggests that reducing sg formation might be a novel therapeutic strategy for ad. We are pushing this work forward on three fronts. 1) we are determining if reducing tia1 inhibits tau pathology and disease progression, and 2) we have identified the proteins that associate with the tau - sg complex, and will be determining which are most important for disease progression.”

“Name of organization or government: new york university school of medicine. (h) purpose of grant: alzheimer's disease research by jorge ghiso, phd entitled: (a2015275s) aging, cerebral amyloid angiopathy, and ab clearance. Investigator's summary: alzheimer's disease, the most common form of dementia, is characterized by the deposition of fibrillar material (amyloid-beta, ab) in brain tissue and cerebral blood vessels. The complex molecular mechanisms involved in the formation and accumulation of these deposits are not well understood although failure in the brain removal of ab is increasingly recognized as a central element in the disease pathogenesis. Our extensive preliminary data indicate that the action of brain enzymes and the clearance of the resulting degradation fragments to the blood and cerebrospinal fluid should not be overlooked as crucial contributors. How brain ab removal is additionally influenced by aging and by the dysfunction of the cerebral microvasculature is the central focus of our proposal. Through the use of state of the art methodologies and genetically engineered mouse models with severe compromise of the cerebral blood vessels the project will provide a better understanding of the brain ab degradation and removal in health and disease, an approach that will likely identify new targets for pharmacologic intervention. Name of organization or government: northwestern university. (h) purpose of grant: alzheimer's disease research by ming-hsuan ou-yang, phd entitled: (a2015289f) paired ig-like receptor b: a novel bace1 substrate. Investigator's summary: bace1 is the enzyme that starts the production of the toxic amyloid-beta (ab) in alzheimer's disease (ad) and drugs that block bace1 to prevent ab production are currently being tested in clinical trials on humans with ad. However, we have discovered that mice lacking the bace1 gene (bace1 knockout mice) that model the effects of bace1 blocking drugs actually have impaired memory, which is the opposite of the intended purpose of drugs for the treatment of ad. We hypothesize that bace1, acting as a pair of molecular scissors, is important for normal memory by cutting and thus controlling the level of pirb, a molecule that is negative regulator of memory function. This study will test this hypothesis so we can better understand the potential side effects of the future bace1 drugs, devise ways to prevent them, and thus ensure to the development of safe and effective bace1 blocking drugs. Name of organization or government: lerner research institute, the cleveland clinic foundation. (h) purpose of grant: alzheimer's disease research by bruce lamb, phd entitled: (a2015296s) the role of trem2 in ad tauopathy. Investigator's summary: we are working to find new drug targets in the brain and to understand the biology of the newly identified immune molecule, trem2, and its role in the alzheimer's disease tau pathology. There are a variety of different cell types in the brain, some of which are normally present, and some of which that are recruited into the brain when it is diseased. We want to better understand the interactions of these cells and identify specific and unique therapeutic targets. Name of organization or government: the regents of the university of california, san francisco. (h) purpose of grant: alzheimer's disease research by jason gestwicki, phd entitled: (a2015297s) regulation of tau homeostasis by molecular chaperones. Investigator's summary: alzheimer's disease is a devastating condition that impacts patients, their families and their caregivers. There are no treatments for this disease, so a major goal of our group is to pursue new and unconventional ways of preventing it. In the current proposal, we are trying to understand how the body's own proteins (termed molecular chaperones) protect us against alzheimer's disease. At the same time, we hope to learn why this system fails during disease, so we can use this knowledge to design drugs that ac”

“Name of organization or government: university of southern california. (h) purpose of grant: alzheimer's disease research by marie-victoire guillot-sestier, phd entitled: (a2015309f) amyloid-beta (ab) clearance by central vs. Peripheral il-10r-/- monocytes. Investigator's summary: innate immune cells function to protect the organism against pathogens, and are divided in two groups: a "central" group located in the central nervous system, and a "peripheral" group in the rest of the body. Alzheimer's disease is defined in part based on accumulation in the brain of a toxic agent called ab that induces memory loss. We will use mice that develop amyloid plaques to study which group of immune cells, "central" or "peripheral", are able to clear the brain of toxic ab peptides. Name of organization or government: johns hopkins university. (h) purpose of grant: alzheimer's disease research by juan troncoso, md entitled:(a2015332s) alzheimer's disease, before plaques and tangles. Investigator's summary: in this application, we propose to study the postmortem brain of individuals between 30 and 50 years of age and to identify those brains with the very early pathologic changes or lesions of alzheimer's disease. Then, we will study whether these lesions are associated with other abnormalities and whether they cause degeneration and death of brain nerve cells. Information obtained from this study could eventually help the development of new diagnostic tests and treatments for alzheimer's disease. Name of organization or government: emory university. (h) purpose of grant: alzheimer's disease research by zhentao zhang, md, phd entitled: (a2015359f) development of aep-related csf markers for ad. Investigator's summary: currently it is very difficult to predict or diagnose alzheimer's disease because there are few reliable biomarkers for this devastating disease. We found that an enzyme named aep is increased in the brain of alzheimer's disease patients. Aep cuts at least two proteins app and tau, generates app and tau fragments, and mediates the onset and progression of alzheimer disease. In the current project we will test whether the concentration and activity of aep as well as the app and tau fragments in the cerebral spinal fluid can serve as biomarkers for the early diagnosis of alzheimer's disease. Name of organization or government: washington university school of medicine. (h) purpose of grant: alzheimer's disease research by celeste karch, phd entitled: (a2015411s) defining the role of phospholipase d3 in alzheimer's disease pathogenesis. Investigator's summary: alzheimer's disease is the most common form of dementia but has no effective prevention or treatment. Understanding how genetic variants that are associated with increased risk for developing alzheimer's disease lead to altered app metabolism and contribute to plaque pathology is essential for developing novel therapeutic targets. We have identified genetic variants in phospholipase d3 that double the risk for late onset alzheimer's disease. The goal of this study is to use cell and mouse models to begin to define the molecular mechanisms by which alzheimer's disease risk variants in <em>phospholipase d3 influence app metabolism and contribute to alzheimer's disease pathology.”

“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, md, phd entitled: (a2015485s) pathological role of amyloid-beta on adipocyte hormone signaling. Investigator's summary: alzheimer's disease is a brain disease that over time causes people to lose memory and have problems with thinking. However, even before the memory and thinking problems occur, people who develop alzheimer's disease start to lose body weight for reasons that are not known. Therefore, our main goal is to study whether there are problems in brain regions that control body weight early on in alzheimer's disease. Once we identify the cause of the weight loss in alzheimer's disease, we will see if this will help us develop new treatments for alzheimer's disease. Name of organization or government: university of south florida. (h) purpose of grant: alzheimer's disease research by daniel lee, phd entitled:(a2015504s) polyamine and arginine metabolism impact tauopathies. Investigator's summary: the tau protein stabilizes microtubules but accumulates in alzheimer's disease and causes neurodegeneration. Arginine decarboxylase is an enzyme that metabolizes the amino acid arginine to make subsequent molecules known as polyamines. We find that increasing other arginine metabolizing enzymes such as arginase 1 decreases tau in the brains of mice. This proposal will identify how arginine decarboxylase regulates tau pathology. Overall, we will identify if increasing arginine metabolizing enzymes and polyamines in the brains of mice impacts tau neuropathology. Name of organization or government: the trustees of columbia university in the city of new york. (h) purpose of grant: alzheimer's disease research by francesca bartolini, phd entitled: (a2015508s) formin-induced stable microtubules in alzheimer's disease. Investigator's summary: extensive evidence suggests that oligomeric ab plays a critical neurotoxic and synaptotoxic role in alzheimer's disease (ad). Our preliminary studies indicate that ab induces subsets of modified stable microtubules and inhibition of this activity prevents synaptic dysfunction. Our proposal relies on a multidisciplinary effort to test the involvement of modified stable microtubules in the pathogenesis of alzheimer's disease and the identification of the key cellular effectors that mediate induction of selective microtubule stability by ab. Our studies will potentially identify new diagnostic markers and introduce a new class of cytoskeleton regulators that may be targeted in drug therapies aimed at rescuing both ab and phospho-tau toxicity in alzheimer's disease. Name of organization or government: university of california, irvine. (h) purpose of grant: alzheimer's disease research by frank laferla, phd entitled: (a2015535s) impact of diabetes on tau pathology and cognition in ad transgenic mice. Investigator's summary: alzheimer's disease (ad) and diabetes mellitus (dm) are two of the most common medical illnesses impacting our society, and recent studies indicate that these two disorders may be related. This proposal seeks to elucidate how diabetes affects ad. As part of this application, we have developed innovative new animals model to dissect the molecular pathways by which of diabetes impacts ad, which is important because elucidating these pathways offers real and concrete opportunities to develop novel therapies.”

“Name of organization or government: vanderbilt university medical center. (h) purpose of grant: alzheimer's disease research by charles sanders, phd entitled: (a2015565s) trem2 and alzheimer's disease. Investigator's summary: trem2 is a protein that plays a major role in helping the brain to cleanse itself of toxic substances that contribute to alzheimer's and related diseases. Defects in this protein make it unable to carry out its job in the brain, leading to the accumulation of toxic hazards. The goal of this work is to take a molecular snapshot of the trem2 molecule (a picture is worth a thousand words) and to examine how it interacts with toxic molecules in the brain. We expect this work to provide information needed to design possible alzheimer's disease treatments that are based on helping trem2 to do its job. Name of organization or government: washington university school of medicine. (h) purpose of grant: alzheimer's disease research by albert davis, md, phd entitled: (a2015577f) apoe regulation of alpha-synuclein pathology. Investigator's summary: in many brain disorders including parkinson disease and alzheimer's disease, certain proteins become clumped, which is harmful to the brain. The factors that influence the clumping of these proteins are not completely known. We believe that a gene which is involved in brain protein clumping in alzheimer's disease may also influence protein clumping and brain injury. This project will study how brain proteins clump and will hopefully pave the way for new treatments for brain diseases including alzheimer's, parkinson's, and related disorders. Name of organization or government: university of california, san diego. (h) purpose of grant: alzheimer's disease research by karen chiang, phd entitled: (a2015595f) effects of pre- and post-synaptic abeta expression on the development of tau pathology. Investigator's summary: tau is an abundant protein found in the brain, which, under normal healthy conditions, contributes to stability of the cytoskeleton. In alzheimer's disease (ad), a small percentage of the total tau in the brain becomes toxic to neurons, and these toxic tau species spread along synaptic connections to different regions of the brain. Previous evidence has implicated the involvement of amyloid-beta (ab), a peptide which is the primary component of the amyloid plaques which characterize ad. Our research intends to study the role of ab in tau toxicity by using transgenic mice expressing both tau and ab in a specific cell population within the hippocampus in order to determine whether tau spread is altered in neurons which form synapses with these ab-expressing cells. Name of organization or government: brigham and women's hospital. (h) purpose of grant: alzheimer's disease research by tracy young-pearse, phd entitled: (a2015607s) screen for modulators of amyloid-beta toxicity in ipsc neurons. Investigator's summary: many past attempts to develop treatments for alzheimer's disease have focused on just one characteristic of the disease-the buildup of a protein known as amyloid-and have assumed that all patients will respond to new treatments in the same way. We have developed a series of laboratory tests that will enable us to look for ways to potentially correct a whole range of problems associated with alzheimer's disease. We also propose using cells derived from several patients in order to determine if individual patients differ in how ad manifests and how they might respond to new treatments. Finally, the project combines a series of modern technologies and a deep understanding of alzheimer's disease that will, for the first time, enable us to answer some very practical questions about ad treatment.”

“Name of organization or government: the trustees of columbia university in the city of new york. (h) purpose of grant: alzheimer's disease research by joseph h lee, dr. P.h. Entitled: (a2015633s) genetic modifiers of the g206a mutation in psen1. Investigator's summary: the main goal of this proposal is to identify new genes that may lead to either earlier or later age at onset of alzheimer disease by examining puerto rican families that have at least one person who carry a unique mutation in the psen1 gene. We will sequence the whole genome, all 3 billion nucleotides, to identify these variants. Based on a small set of samples, we have already identified a few genes that may modify age at onset of alzheimer disease, and in this study, we will extend the study to a larger set of families. This study may identify genetic variants that may point to potential therapeutic targets that could alter the age at onset of alzheimer's disease. Name of organization or government: university of south florida. (h) purpose of grant: alzheimer's disease research by umesh jinwal, phd entitled: (a2015666s) investigating the role of cdc37 co-chaperone in ad pathogenesis. Investigator's summary: abnormalities in tau protein have been linked to alzheimer's disease (ad) and several other neurodegenerative diseases. These diseases are becoming more and more prevalent in our aging population. This proposal is aimed to provide novel insight into tau abnormalities via alteration of a chaperone protein cdc37 in cellular and animal models of ad. Name of organization or government: university of florida. (h) purpose of grant: alzheimer's disease research by jada lewis, phd entitled: (a2015688s) towards a knockdown therapy for tauopathy. Investigator's summary: we propose a research where using genetically modified mice carrying p301l mutation, alteration associated with the neurodegenerative disease frontotemporal dementia, we will apply two techniques known as knock-down which uses complementary rna to specific sites of that specific mutation as tool to block the altered protein and the other approach is cut dna at specific regions of tau protein with the purpose of express less amount of the tau protein with the purpose of curing the familial ftd. Name of organization or government: university of alabama at birmingham. (h) purpose of grant: alzheimer's disease research by erik roberson, md, phd entitled: (a2015693s) development of inhibitors of the tau-fyn interaction for the treatment of alzheimer's disease. Investigator's summary: the purpose of this project is to identify a novel therapy for treating alzheimer's disease. We are investigating compounds that would stop the interaction between two proteins, tau and fyn. Considerable data indicates that blocking this interaction could ameliorate alzheimer's disease.”

“Name of organization or government: dana-farber cancer institute. (h) purpose of grant: alzheimer's disease research by kimberly, glass, phd entitled: (c2014001) 21st century brain trust award: sex specific difference in alzheimer's disease are characterized by unique alterations in cellular network structure. Investigator's summary: big data approaches stand to contribute much to knowledge of alzheimer's disease. This project focuses computational expertise on understanding the influence of gender on development of alzheimer's disease. Name of organization or government: anthrotronix, inc. (h) purpose of grant: alzheimer's disease research by corinna lathan, phd entitled: (c2015001)defense automated neurobehavioral assessment for mild dementia pilot study. Investigator's summary: this grant test battlefield technologies for post-injury cognitive assessment in the context of alzheimer's disease, testing whether automated cognitive testing might be informative in identifying or monitoring in this population. Name of organization or government: alzheimer's drug discovery foundation.(h) purpose of grant: alzheimer's drug discovery foundation access platform. Summary: service to pair academic researchers with contract research organizations. Name of organization or government: global alzheimer's platform, inc. (h) purpose of grant: alzheimer's disease research entitled: (c2015300) public private partnership to foster innovative clinical trials in alzheimer's disease. Summary: by linking existing registries and developing standing cohorts of research-ready trial participants, this project hope to offset the challenges in recruiting subjects to alzheimer's disease clinical trials.”

“Name of organization or government: the cleveland clinic foundation. (h) purpose of grant: national glaucoma research by john w crabb, phd entitled: (g2015039) proteomic approaches to poag mechanisms & biomarkers. Investigator's summary: glaucoma is an age-related ocular disease and leading cause of blindness. While age and intraocular pressure (iop) are major risk factors for the development of primary open angle glaucoma (poag), eye doctors cannot yet predict who will develop poag. The identification of additional risk factors is a high priority. The proposed research will identify glaucoma-altered proteins in the clear fluid at the front of the eye (i.e., aqueous humor) that will lead to improved understanding of disease mechanisms and the identification of biomarkers that will assist in caring for glaucoma patients. Name of organization or government: the university of texas medical branch at galveston. (h) purpose of grant: national glaucoma research by yonju ha, phd entitled: (g2015044) the role of cxcl10/cxcr3 in neurodegeneration during glaucoma. Investigator's summary: glaucoma is the second leading cause of blindness by retinal neuronal cell death in the worldwide and it occurs by increasing of pressure in the eye. However, the treatment of lowering eye pressure is not always effective on preventing the progression of glaucoma. Therefore, we will test whether two proteins called cxcl10 and cxcr3 are involved in retinal inflammation and neuronal cell death during glaucoma. Our final goal is to develop novel therapeutic approach to protect glaucoma patients from blindness, for example, by inhibiting the functions of cxcl10 and cxcr3. Name of organization or government: regents of the university of california, davis. (h) purpose of grant: national glaucoma research by vijay krishna raghunathan, phd entitled: (g2015078) steroid induced modulation of extracellular matrix. Investigator's summary: steroids, routinely used to control inflammation, can cause increases in intraocular pressure and threaten a loss of vision in 30-40% of all individuals. What causes such increases in pressure and why only a subset of individuals respond adversely to steroids is not known. We believe that such increases in pressure are due to dysregulation in cellular function, in secretion of proteins, and due to structural alterations to the tissue that the cells are in close proximity with. In the proposed study, we will determine if treatment with steroids alters cellular and matrix structure, composition, biomechanical attributes, and function. Name of organization or government: duke university. (h) purpose of grant: national glaucoma research by guorong li, md entitled: (g2015100) oct measurement of tm/sc stiffness in living mice. Investigator's summary: the most important issue for preventing blindness in glaucoma patients is early diagnosis and effectively treatment of the disease. We have developed a way to visualize the movement of mouse outflow pathway, tissues controlling intraocular pressures at different pressures and glaucoma drug treatments without touching the eye. This project is vital in three ways: 1) we can make glaucoma eyes in mice that mimics the disease in patient to test how diseased eyes are different from normal eyes in outflow tissues; 2) we can treat the glaucoma eyes with newly developed drug to see how safe and effective of the drug to treat glaucoma eyes; 3) the information collected from the animals can be applied to clinic for glaucoma early diagnosis and effective treatment.”

“Name of organization or government: university of alabama at birmingham. (h) purpose of grant: national glaucoma research by rafael grytz, phd entitled: (g2015115) quantifying collagen remodeling of the optic nerve head. Investigator's summary: glaucoma is a leading cause of blindness and the progressive remodeling and excavation of the connective tissues of the optic nerve head is a common feature of all glaucoma phenotypes, yet little is known about the underlying mechanisms. To study growth and remodeling mechanisms in glaucoma is very challenging, as the underlying mechanisms occur at very different length scales (from an elevated intraocular pressure at the organ level to a potential alteration of the collagen fibril structure at the micro-scale). Also, the optic nerve head, the site of initial axonal damage in glaucoma, is not directly accessible for imaging as other tissues surround it. We propose to develop a novel imagining and quantification methodology, and to use this methodology together with a new animal model to gain insight into the growth and remodeling mechanisms that underlie glaucoma. Name of organization or government: johns hopkins university. (h) purpose of grant: national glaucoma research by thao nguyen, phd entitled: (g2015132) biomechanics of the optic nerve head: measuring the effects of chemical treatments altering connective tissue properties. Investigator's summary: intraocular pressure is a major risk factor for the development and severity of glaucoma. This project investigates the biomechanical environment of human optic nerve head caused by intraocular pressure to understand the connection between pressure and glaucoma. Moreover, the project aims to measure how the biomechanical environment of the optic nerve head can be altered by chemical treatments that stiffen or soften the eye-wall for neuroprotection. The implications of this work can be important to understanding the susceptibility of individuals to glaucoma, to developing new diagnostics techniques, that for example measure a key mechanical property of the sclera and lamina cribrosa, and to developing new therapeutic strategies. Name of organization or government: university of north texas health science center. (h) purpose of grant: national glaucoma research by adnan dibas, phd entitled: (g2015163) targeting asics in optic neurodegenerative diseases is neuroprotective. Investigator's summary: glaucoma is the second cause of blindness in the us. Currently, glaucoma drugs only lower pressure in the eye, however, vision loss continues. Therefore, there is an urgent need for newer drugs that can save the neurons in the eye following any eye injury. The current project will attempt developing such novel drugs. Name of organization or government: icahn school of medicine at mount sinai school of medicine. (h) purpose of grant: national glaucoma research by audrey bernstein, phd entitled: (g2015195) exfoliation syndrome and lysosomal disease. Investigator's summary: in exfoliation syndrome (xfs), the eye starts accumulating 'white fluff' deposits composed of protein aggregates. The aggregates eventually block the exit of fluid from the eye, causing a buildup of pressure that can lead to blindness. We have discovered that cells obtained from xfs eyes may have a problem degrading these protein aggregates leading to an accumulation of "cellular trash" that becomes toxic. In this proposal we will test methods to accelerate degradation of this cellular waste to improve the health of xfs cells.”

“Name of organization or government: the regents of the university of michigan. (h) purpose of grant: national glaucoma research by julia richards, phd entitled: (g2015202) genetics of homocysteine metabolism in glaucoma. Investigator's summary: cysts in the iris can block the ability of fluid to flow out of the eye, leading to build up of pressure in the eye and glaucoma (damage to the optic nerve). We will study a new angle closure glaucoma gene, mtrr, that we found by studying a large family with iris cysts. We will do biochemical and functional studies of the protein that has been changed by the mutation. We will also study the role of the normal protein in the eye. We will screen for mutations in this gene in a different, common form of glaucoma with which this biochemical pathway has been associated. These investigations will begin detailing the role of homocysteine metabolism in glaucoma and may lead to the development of future therapies. The discovery of this new angle closure glaucoma gene has raised the possibility that we might be able to develop dietary interventions to prevent or limit the severity of types of glaucoma that involve homocysteine metabolism. Name of organization or government: stanford university. (h) purpose of grant: national glaucoma research by jeffrey goldberg, md, phd entitled: (c2015201) phase ii glaucoma clinical trial. Investigator's summary: this randomized controlled trial will test the efficacy and safety of a neuoprotection candidate drug in glacuoma. Name of organization or government: georgia tech foundation. (h) purpose of grant: national glaucoma research by ross ethier, phd entitled: purchase of oct imaging system. Investigator's summary: supplement to collaborative grant in glaucoma. Name of organization or government: duke university. (h) purpose of grant: macular degeneration research by goldis malek, phd entitled: (m2015421) the role of a macrophage chemotactic factor in amd. Investigator's summary: age-related macular degeneration is a devastating disease resulting in blindness in the elderly. Though what causes it is still unknown, we know that the immune system is involved. The experiments in this study are designed to address the following question: what is the role of a specific factor called osteopontin, that may be responsible for recruiting immune cells to eye, in development and progression of age-related macular degeneration? The answer may result in identification of a future target for therapy.”

“Name of organization or government: university of florida. (h) purpose of grant: macular degeneration research by qiuhong li, phd entitled: (m2015178) ang-(1-7)/mas signaling in aging eye- protective mechanisms and therapeutic potential. Investigator's summary: age-related macular degeneration is multifaceted degenerative retinal disease involving complex pathologic pathways, and it so far incurable. We have identified a new signaling pathway that will block multiple pathologic pathways implicated in amd and promote endogenous protective pathway. The overall goals of this proposed research to study the protective mechanism of this new signaling pathway and its downstream target gene, and to test their therapeutic efficacy in animal models of amd. Name of organization or government: university of north texas health science center. (h) purpose of grant: macular degeneration research by hongli wu, phd entitled: (m2015180) the role of glutaredoxin 2 (grx2), a mitochondrial thiol repair enzyme, in age-related macular degeneration. Investigator's summary: too many free radicals (bad molecules created by oxidation) in the retina is believed to cause age-related macular degeneration (amd). Glutaredoxin 2 (grx2) is a newly discovered antioxidant enzyme, which can break down free radicals in the retina. In this project, we will study if and how grx2 protects retinal pigment epithelial cells against free radicals. Results from this study may lead to a better treatment for amd. Name of organization or government: the schepens eye research institute. (h) purpose of grant: macular degeneration research by yin shan ng, phd entitled: (m2015214) tlr2 as a novel therapeutic target for cnv pathogenesis. Investigator's summary: although current therapies for choroidal neovascularization (cnv) associated with age-related macular degeneration are effective in the short term, they are expensive, they address the symptoms rather than the cause of the disease, and concerns have been raised about their long-term efficacy and safety. The objective of this proposal is to validate the functional role of toll-like receptor 2 (tlr2), a component of the innate immune system, in cnv pathogenesis, and to evaluate tlr2 as a novel, effective and safe therapeutic target for the treatment of cnv. Name of organization or government: johns hopkins university. (h) purpose of grant: macular degeneration research by noriko esumi, md, phd entitled: (m2015220) increasing stress resistance: a new strategy for amd. Investigator's summary: age-related macular degeneration (amd) is the leading cause of blindness in elderly people worldwide, and the retinal pigment epithelium (rpe) is the primary site of damage for developing amd. Chronic inflammation and oxidative stress are recognized as important underlying factors that lead to amd. Therefore, molecules that can reduce inflammation and/or increase resistance to harming stresses in the rpe seem to provide a new strategy against this devastating blinding disease. This study aims to evaluate the potential of such a candidate molecule for prevention and treatment of amd.”

“Name of organization or government: duke university. (h) purpose of grant: macular degeneration research by mikael klingeborn, phd entitled: (m2015221) the role of exosomes in dry amd. Investigator's summary: at present there is no way to treat the dry form of age-related macular degeneration (amd) which eventually leads to blindness. The experiments i am proposing are aimed at understanding more about what makes retinal pigment epithelium (rpe) cells in the eye sick in the amd disease process and how small lipid vesicles that rpe cells release may be involved. The result from these experiments may help us find new drugs to treat sick rpe cells in eyes of people with amd and in so doing save their eyesight. Name of organization or government: university of rochester medical center. (h) purpose of grant: macular degeneration research by ruchira singh, phd entitled: (m2015267) delineating the role of ecm alterations in a patient-derived hipsc-rpe-ec co-culture model of macular degeneration. Investigator's summary: delineating the role of ecm alterations in a patient-derived hipsc-rpe-ec co-culture model of macular degenerationin macular degeneration, the light-sensing tissue in the back of our eye, called the retina, is affected. In the retina, the retinal pigment epithelium (rpe) cells and their underlying vascular support system, the choroid, are the main cell types affected in age-related macular degeneration (amd) and similar diseases. However, it is not known whether rpe or choroid cells are responsible for the disease. Therefore, our goal in this study is to identify whether loss of rpe or choroid cell function alone can cause the disease. This knowledge will help us to develop drug treatments that can make the affected cell type healthy again. Name of organization or government: indiana university school of medicine.(h) purpose of grant: macular degeneration research by timothy corson, phd entitled: (m2015301) novel antiangiogenic compounds for treatment of choroidal neovascularization. Investigator's summary: abnormal blood vessel growth in the eye causes "wet" age-related macular degeneration, a major cause of blindness. Since many patients do not respond to existing therapies, new drugs are needed to block this blood vessel growth. Starting with a new chemical that we developed that blocks blood vessel growth, we will design and produce related chemicals that are even more potent and selective for blood vessel cells over other cell types. We will then determine the best dosage regimen for two of these compounds to maximize their levels and effects in the eye, en route to developing a new therapy for this disease. Name of organization or government: university of florida. (h) purpose of grant: macular degeneration research by alfred lewin, phd entitled: (m2015348) a novel antioxidant therapy for retinal degeneration. Investigator's summary: toxic oxygen compounds are known to damage the retina with age and to contribute to age related macular degeneration (amd). We will use a mouse model of dry amd to test a potent antioxidant compound that we characterized previously to determine if it prevents retinal degeneration in these mice. Our goal is to prevent progression of dry amd in people with early signs of this blinding disease.”

“Name of organization or government: board of regents of the university of wisconsin system. (h) purpose of grant: macular degeneration research by aparna lakkaraju, phd entitled: (m2015350) can rpe-derived exosomes contribute to subretinal drusenoid deposits?. Investigator's summary: over 11 million americans currently suffer from age-related macular degeneration, the most common cause of irreversible vision loss among older adults. With age, insoluble aggregates accumulate above and beneath the retinal pigment epithelium, the tissue that nourishes and supports the photoreceptors, the light-sensing cells of the eye. Over a lifetime, these aggregates conspire with environmental and genetic factors to damage the pigment epithelium and lead to a chronic decline in vision. Our work seeks to understand how these aggregates form, how they impact cell function and whether a promising treatment strategy recently identified by our group will help prevent the formation of these aggregates and preserve healthy vision. Name of organization or government: medical university of south carolina. (h) purpose of grant: macular degeneration research by ernesto moreira, md entitled: (m2015356) using induced pluripotent stem cell-derived retinal pigmented epithelium to study the effects of oxidative stress and complement activation in age-related macular degeneration in vitro. Investigator's summary: the retinal pigmented epithelium (rpe), a layer of cells under the light capturing photoreceptors, plays a crucial role in the development of age-related macular degeneration (amd). In this project, we will utilize stem cell technology to further understand how toxins derived from smoking lead to rpe damage through the activation of immune complement system. The utilization of stem cells offers a clear advantage over current models, because we can derive tissues from amd patients, which carry the genetic background of the disease. This will allow us to directly investigate the immune complement system in genetic conditions of amd, thereby providing a better understanding of disease mechanisms and the ability to test potential therapeutic interventions. Name of organization or government: university of california, davis. (h) purpose of grant: macular degeneration research by marie burns, phd entitled: (m2015379) high-resolution in vivo imaging for early detection and treatment of retinal degeneration. Investigator's summary: blindness is commonly caused by death and disappearance of light-sensing cells in the retina. One big-picture goal of our research is to identify cells in distress and to heal them before they die and before patients lose their sight. Because doctors have the ability to look inside the eye as part of routine exams, our research is developing new ways to image cells in the living eye, providing a new "window to health", with the ultimate goal to delay or prevent blindness through early detection. Name of organization or government: university of california, los angeles.(h) purpose of grant: macular degeneration research by steven nusinowitz, phd entitled: (m2015295) scotopic critical flicker fusion in preclinical amd. Investigator's summary: if we are going to be able to treat people at the earliest stages of macular degeneration (amd) before they have permanent damage, we need to be able to identify those people who would benefit from a preventive treatment. Genetic testing alone is not sufficient to know who will develop amd and we are testing the possibility that an early indication that a person may develop or is developing amd is the impairment of the ability of the retina, particularly the cells that detect low levels of light, to rapidly recover from light exposure. We are developing a simple test for this response to flickering lights that can be done at multiple locations in the retina. We will determine if this test can be used to help in the prediction of those who will develop amd and/or distinguish different form of amd”

“Name of organization or government: johns hopkins university. (h) purpose of grant: macular degeneration research by noriko esumi, m.d., ph.d. Entitled: (m2012044) efficient differentiation of retinal pigment epithelial cells from human embryonic stem cells. Investigator's summary: supplement to research grant in amd. Name of organization or government: dean mcgee eye institute. (h) purpose of grant: retinal degeneration meeting grant. Summary: the retinal degneration meeting exists to facilitate knowledge sharing amongst researchers in the amd community and other retinal disorders. Name of organization or government: helen keller foundation for research & education. (h) purpose of grant: helen keller prize for vision research partnership. Summary: the helen keller prize for vision research recognizes significant accomplishments in vision research, and provides funds for continuance of those studies.”