2012-05-04T16:14:13-05:00 2011-12-31 042824790 John A Epeneter PC 1 Marginal Way Springvale ME 04083 990 2011-01-01 522396428 Alzheimer's Disease Research Foundation Cure Alzheimer's Fund ALZH 7812373800 34 Washington Street No 200 Wellesley MA 02481 timothy w armour 8772873259 2012-05-04 1 P00637532 2074597803 2011 2016-02-24 21:20:13Z Timothy W Armour 21 Sunset Road Weston MA 02493 4687274 0 X www.curealzfund.org X 2004 PA To fund research with the highest probability of preventing, slowing or reversing Alzheimer's disease. 6 5 6 6 0 0 3983161 4682190 0 0 -5755 5084 0 0 3977406 4687274 3394263 2052500 0 0 305410 445931 0 0 267051 382718 624839 4082391 3123270 -104985 1564004 3273139 4601371 318936 50903 2954203 4550468 X To fund research with the highest probability of preventing, slowing or reversing Alzheimer's disease. 0 0 600000 See Schedule O for description.The Alzheimer's Genome Project (AGP) has been Cure Alzheimer's Fund signature research effort for several years. The objective is to identify all genes confirming risk for or protection against Alzheimer's disease.In 2011 Cure Alzheimer's Fund distributed $2,117,823 for research support projects. To read a more detailed report on our research, see Cure Alzheimer Fund's Scientific Report 2011.AGP; Massachusetts General Hospital; Dr. Rudy Tanzi;Since starting the project, over 120 Alzheimer's gene candidates have been identified. The AGP now continues with the objective of a) confirming which of those candidate genes are actual Alzheimer's genes, and b) understanding how they affect Alzheimer's pathology. 100000 Molecular Tweezers: Novel Inhibitors of amyloidogenic porteins and promising drug candidates for Alzheimer's disease; Gal Bitan; University of California, Los Angeles.We propose a focused program that will allow us to plan expanded in vivo characterization of the efficacy of novel compounds called "molecular tweezers,"which modulate the aberrant assembly process using a heretofore-unexplored "process-specific" mechanism towards development of disease-modifying therapy for AD and related diseases. 408104 Program service costs, such as an allocated portion of program salaries, fringe benefits, information and awareness, SAB/RC support, and similar direct program costs that have not been specifically allocated to the amounts of specific grant expenditures. 100000 Modulation of Abeta Deposition by Cell-Specific Mechanisms; University of Chicago; Dr. Sangram Sisodia.The specific aims of this proposal are to employ genetic and molecular strategies to conditionally delete Familial Alzheimer's disease (FAD)-linked mutant transgenes in specific cell types of the Central Nervous System in order to explore the effects of this manipulation on Abeta deposition. 150000 Novel Soluable Gamma-Secretase Modulators; Steven Wagner; University of California, San Diego.Many investigators have explored Gamma-secretase modulators (GSMs) as ways of affecting Abeta production and therefore interrupting the earliest stages of Alzheimer's pathology. One reason for the lack of success in this area has been that earlier GSMs were insoluble. We propose to synthesize a photoaffinity probe based on the most potent Soluble Gamma-Secretase Modulator compound that we have developed which will be used in photolabeling and affinity capture experiments in order to provide direct evidence for the molecular target of these AGSMs. These photoaffinity-labeling and affinity capture studies using the SGSM photoprobe will be carried out in collaboration with Dr.Rudy Tanzi using various reconstituted and well charcterized y-secretase assay systems as described previously. 100000 Effect of Bexaratene on Abeta in Alzheimer's disease; Washington University, St. Louis; David Holtzman.We will assess the efects of bexarotene, a drug originally developed to treat a rare type of lymhoma, on interstitialfluid AB levels over hours as well as its effects on behavior and AB deposition and associated pathology over weeks and months. This will confirm and extend results from the laboratory of Gary Landreth at Case Western Reserve University whose work on bexarotene suggests it may be particularly effective as a treatment for Alzheimer's disease. 150000 Optimization of Novel ACAT Inhibitors for Alzheimer's Disease; Dora M. Kovacs; Massachusetts General Hospital.We have recently designed and screened a library of 45 novel ACAT inhibitors, based on the structure of CI-1011. From this screen, we have identified three novel ACAT inhibitors that reduce AB generation. Here we will optimize these three inhibitors by screening a novel library of compounds based on their structure. We will determine whether the novel inhibitors prevent development of amyloid pathology and alter APP process in AD mice in absence of toxicity. These studies should result in one or more novel ACAT inhibitors with the potential to prevent and treat AD. 100000 Structural and Functional Analysis of Novel Abeta and Tau Oligomers Using Conformation-specific Monoclonal Antibodies; George S. Bloom, Ph.D.; University of Virginia, Charlottesville, Virginia.The specific goals of this project are to determine if any of the antibodies developed in the laboratory of Charles Glabe, UC-Irvine, recognize the beta-amyloid or tau oligomers that the Bloom lab is studying, and whether the antibodies can prevent formation of those oligomers. Completion of this work could lead eventually to new diagnostic and therapeutic tools for AD. 100000 Cellular and Animal Models of Amyloid Pathology in Early Alzheimer's Disease; Charles Glabe, Ph.D.;University of California, Irvine, California.The significance of this work is the identification of the earliest type of amyloid pathology in the beginning of the disease and the discovery of a novel mechanism for amyloid pathogenesis. This may provide a new target for therapeutic development and provide evidence for the early. 100000 Exploring Adult Neurogenesis as a Therapeutic Target for Alzheimer's Disease; Se Hoon Choi, Ph.D.; Massachusetts General Hospital, Boston, Massachusetts.Recent evidence shows that the adult brain contains discrete populations of stem cells that retain the capacity to generate new neurons through the process of neurogenesis. We will test whether the strategy of stimulation of endogenous stem cells in the AD brain is safe and effective ultimately to find treatment for Alzheimer's patients. 100000 Alzheimer's Disease Models Based on Human Neuronal Progenitor Cells; Doo Yeon Kim, Ph.D.; Massachusetts General Hospital, Boston, Massachusetts.We propose to develop Alzheimer disease models based on human neural progenitor cells. Human neural progenitor cells are multipotent stem cells that can differentiate to brain cells in in vitro and in vivo conditions. In this study, we will develop genetically modified human neural progenitor cells that can replicate Alzheimer's disease pathology in in vitro and in vivo conditions. Our study will provide a novel Alzheimer's disease model system that can be used to develop and test Alzhemier's disease drugs in human brain cells. Our study will also provide a human Alzheimer's disease model for basic researches. 100000 Role of ADAM10 in the Pathogenesis of Alzheimer's Disease After Head Trauma; Dr. Giuseppina Tesco; Tufts University School of Medicine, Boston, Massachusetts.Traumatic brain injury (TBI) is the strongest environmental risk factor for the development of Alzheimer's Disease (AD). In addition, cleavage of the APP protein by a-secretase gives rise to the production of the secreted alph cleaved APP fragment (sAPPa), which has been shown to have neuroprotective properties. A recent study has shown that when synthetic sAPPa is administered to mice following experimental head trauma it appears to be protective, reducing neuronal death and axonal injury. If the neuroprotective properties of sAPPa following head trauma can be confirmed, this provides a potential therapeutic strategy for improving a patient's clinical outcome and reducing the potential for the development of AD following head trauma. 100000 Metallomic Mapping of the Aging Brain in the Trg2576 Mouse model; Dr. Lee Goldstein; Boston University, Boston, Massachusetts.Zinc and other key brain biometals play a critical role in normal brain function, and when altered, development of Alzheimer's disease. Recent clinical trials strongly support development of drugs targeting brain biometals and metal-protein interactions as a promising therapeutic stragegy for this devastating neurodegenerative disease. In this project, Dr. Goldstein will deploy unique analytical resources at the Boston University center for Biometals & Metallomics to perform the first high-resolution metallomic brain maps of key biometals (copper, zinc, iron) during normal brain aging and Alzheimer's disease. 100000 Selective Cell Vulnerability in Alzheimer's Disease; Dr. Paul Greengard; The Rockefeller University, New York City, New York.The Greengard Laboratory recently developed a new procedure to compare the molecular profiles of very specific cell types inside the brain. They will apply this technology in order to compare vulnerable regions with more resistant regions that don't show any pathology until late stages of the disease. 50000 Understanding the up-regulation of Neurosperpin in Alzheimer's disease brain and isolating a potential therapeutic inhibitor of its action; a continuation. Dr. Nicholas Seeds; University of New Mexico.Specific aim #1 for the project is to determine what is responsible for the up-regulation of neuroserpin in the Alzheimer's disease brain. Specific aim #2 for the project is to use a sensitive high throughput assay screen for inhibitors of neuroserpin to a) screen commercially available libraries and selected chemical compounds, b) use medicinal chemistry to optimize and design new molecules based on the structures of identified hit candidate molecules (above) and crystal structure of neurserpin, c) confirmation of screening "hits", rule out false positives, do dose response curves and counter-screens to identify "leads", and d) test for "hit" interaction with neuroserpin, possible mechanism of action and potential toxicity in hippocampal neuronal cell cultures. 65323 Documentary ProjectIndependent video producer and author of books and articles on Alzheimer's disease, David Shenk, has obtained support from the MetLife Foundation for underwriting several short videos on Alzheimer's from the patient and care-giver perspective. Shenk and Metlife have asked Cure Alzheimer's Fund to serve as fiscal agent for the project with all editorial and production responsibility residing with Shenk. Cure Alzheimer's Fund receives funds from MetLife and disburses them by invoice upon request by Shenk. The estimated budget is $372,000 and the amount disbursed during 2011 was $65,323. 2500 AlzGene ProjectThe AlzGene database (www.alzgene.org) is a revolutionary resource for Alzheimer's researchers providing data and meta-analyses from hundreds of genetic association studies in an easy-to-use, searchable, web-based database. This site allows researchers to post their findings and comment on other findings. It aggregates huge amounts of information that will help in the search for the genetic makeup of Alzheimer's. Currently, the database has more than 1,000 studies. The site also contains a continuously updated list displaying the genes most strongly associated with AD (on the website see "Top AlzGene Results"). Scientists interested in a particular gene can search for it in AlzGene to see what previous studies have reported, receiving a wealth of information in a very short amount of time. 2011 expenses were for web maintenance. 100000 Mechanisms of Retinoid X Receptor-mediated Abeta Clearance in Ad; Gary Landreth; Case Western Reserve University; This application represents collaboration between the laboratories of Dr. David Holtzman, Rudolph Tanzi and Gary Landreth that is focused on investigating the mechanisms through which RXRs promote amyloid clearance from the brain. The Landreth lab will specifically determine if RXR agonist treatment of murine models of AD provokes the conversion of microglia from a proinflammatory state into alternative M2 states that are associated with tissue repair and induction of phagocytic functions, all contributing to evidence that the drugbexarotene, originally developed to treat a rare form of lymphoma, is effective against Alzheimer's disease. 1417823 2525927 1 1 0 1 0 0 0 0 0 1 0 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 1 0 1 0 0 0 0 0 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 0 6 1 0 0 0 0 0 0 0 0 X 6 5 1 0 0 0 0 0 0 1 1 1 0 1 1 1 1 1 1 1 0 0 MA AL AK AS AZ AR CA CO CT DE DC FM FL GA GU HI ID IL IN IA KS KY LA ME MH MD MI MN MS MO MT NE NV NH NJ NM NY NC ND MP OH OK OR PW PA PR RI SC SD TN TX UT VT VI VA WA WV WI WY X X Timour W Armour 7812373800 34 Washington Street Suite 200 Wellesley Hills MA 02481 X Jeffrey Morby 2.00 X 0 0 0 Jacqueline Morby 5.00 X 0 0 0 Henry McCance 1.00 X 0 0 0 Phyllis Rappaport 1.00 X 0 0 0 John S Lazo PhD 1.00 X 0 0 0 Timothy W Armour 40.00 X 194257 0 0 Katherine F Cutler 30.00 X 12570 0 0 Michael FCurren 40.00 X 88846 0 0 Sally G Rosenfield 40.00 X 83462 0 0 379135 0 0 1 0 1 0 0 4682190 626188 4682190 1132 1132 623688 619736 3952 3952 3952 4687274 3952 0 1132 2052500 2052500 398173 135701 138241 124231 47758 13947 19306 14505 2768 2768 40609 40609 10795 1670 9125 2806 2806 5836 5836 34707 34707 30931 16050 13137 1744 6937 886 3222 2829 8995 8995 1872 1872 Information and awarene 187635 187635 Documentaries 65323 65323 Public relations 49931 49931 Government relations 36000 36000 139694 17885 59929 61880 3123270 2525927 330292 267051 654165 1328315 2343857 3029460 15267 219843 192993 3810 1762 50525 24005 13813 26520 386 308 21998 22013 3273139 4601371 307585 31531 11351 19372 318936 50903 X 0 0 0 0 0 1596265 2954203 4550468 3273139 4601371 X 1564004 32261 X 0 1 1 X 0 X 3560203 3042089 3339366 4039719 4763246 18744623 3560203 3042089 3339366 4039719 4763246 18744623 7470070 11274553 97016 74626 20020 -5755 5084 190991 -498 -498 18935116 0.59540 0.58230 X RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED RESTRICTED 0 0 0 0 0 0 1 41032 0 0 41032 0 Explanation of Other Lobbying Activities: Part II-B, Line 1i: A registered lobbyist contacted various Congressional legislators for the purpose of encouraging increased funding of Alzheimer's disease research. 24377 11787 12590 26148 12218 13930 26520 Accrued payroll 18507 403b employee contributions 865 19372 4687274 3123270 1564004 32575 -314 32261 1596265 4428125 -314 32575 80823 113084 4315041 372233 372233 4687274 3123270 32575 32575 3090695 32575 32575 3123270 Description of Uncertain Tax Positions Under FIN 48: Part X: Part X, Line 2: Income Taxes - CAF was determined to be exempt from federal income tax under provisions of Section 501(c)(3) of the Internal Revenue Code of 1986 (IRC) and has been classified as an organization that is not a private foundation as defined in Section 509(a)(3) of the IRC. Accordingly, no provisions for federal or state income taxes are required. CAF is required to recognize the financial statement impact of a tax position when it is more likely than not that the position will be sustained upon examination. Any interest and penalties recognized associated with a tax position would be classified as current in CAF's financial statements. Currently, the tax years ended December 31, 2007, 2008, and 2009 are open and subject to examination by the Internal Revenue Service and the Massachusetts Department of Revenue. However, CAF is not currently under audit nor has CAF been contacted by any of these jurisdictions. Based on the evaluation of CAF's tax positions, management believes all positions taken would be upheld under an examination. Therefore, no provision for the effects of uncertain tax positions has been recorded for the year ended December 31, 2011. Part XI, Line 8 - Other Adjustments: Unrealized gains (losses) on investments -314. 0 Massachusetts General Hospital MGH Aging and Research Unit 114 16th Street Charlestown MA 02129 501c3 600000 Continuation of Alzheimer's Genome Project Massachusetts General Hospital MGH Aging and Research Unit 114 16th Street Charlestown MA 02129 501c3 150000 Optimization of Novel ACAT Inhibitors Massachusetts General Hospital MGH Aging and Research Unit 114 16th Street Charlestown MA 02129 501c3 100000 Alzheimer's Disease Models Based on Human Neuronal Progenitor Cells Massachusetts General Hospital MGH Aging and Research Unit 114 16th Street Charlestown MA 02129 501c3 100000 Exploring Adult Neurogenesis as a Therapeutic Target for Alzheimer's Disease Washington University at St Louis 660 S Euclid Avenue St Louis MO 63110 501c3 100000 Effect of Bexaratene on Abeta in Alzheimer's disease Case Western Reserve University 10900 Euclid Avenue Cleveland OH 441067043 501c3 100000 Mechanisms of Retinoid X Receptor-mediated Abeta Clearance in AD University of California Los Angeles 405 Hilgard Avenue Los Angeles CA 90095 501c3 100000 Molecular Tweezers: Novel Inhibitors of amyloidogenic proteins and promising drug University of California San Diego 9500 Gilman Drive La Jolla CA 92093 501c3 150000 Novel Soluble Gamma-Secretase Modulators for the Treatment of Alzheimer's The University of Chicago School of Medicine Chicago 5841 South Maryland Avenue Chicago IL 60637 501c3 100000 Modulation of Abeta Deposition by Cell-Specific Mechanisms The Rockefeller University 1230 York Avenue New York NY 10065 501c3 100000 Selective Cell Vulnerability in Alzheimer's disease University of Virginia PO Box 800793 Charlottesville VA 22908 501c3 100000 Structuraland Functional Analysis of Novel Abeta and Tau Oligomers Using Conformation specific University of California Irvine Medical Center 101 The City Drive Orange CA 92868 501c3 100000 Cellular and animal models of amyloid pathology in early Alzheimer's disease University of New Mexico 1 University of New Mexico Albuquerque NM 87131 501c3 50000 Understanding the up-regulation of Neurosperpin in AD diseased brain Tufts University School of Medicine 145 Harrison Avenue Boston MA 02111 501c3 100000 Role of ADAM10 in the pathogenesis of AD after head trauma Boston University 700 Albany Street Boston MA 02118 501c3 100000 Metallomic Mapping of the Aging Brain in the Trg2576 Mouse Model 15 15 Schedule I,Part I, Line 2 1 X 0 0 0 0 0 0 0 0 0 Timothy W Armour 184257 0 10000 0 0 0 0 0 0 0 194257 0 0 0 Part I, Line 1b None of the above fringe benefits are paid. Part I, Line 3 A compensation committee reviews all compensation annually. X 11 623086 average high and low X Services 1 32575 Invoice amount 0 0 0 Form 990, Part VI, Section A, line 2 Jeffrey Morby and Jacqueline Morby are both directors and marriage partners. Form 990, Part VI, Section B, line 11 The President reviews the Form 990 prepared by the organization's controller before providing copies to the directors, and if necessary, will consult with legal counsel. Form 990, Part VI, Section B, line 12c The President regularly and consistently monitors compliance with conflicts of interest by requesting that all officers, directors, and founders sign the annual statement disclosing all interests that might conflict with any interest of the organization. Form 990, Part VI, Section B, line 15a Comparability data are submitted annually to executive committee for compensation approval for the President and all other employees. Form 990, Part VI, Section C, line 18 The governing documents, conflict of interest policy and financial statements are made available on the organization's website and upon request. Form 990, Part VI, Section C, line 19 The organization's governing documents are available upon request. PART 7, SECTION A Henry McCance, 2300 North Scenic Highway, Lake Wales, FL 33898 Jeffrey and Jacqueline Morby, 18 South Island Drive, Key Largo, FL 33037 Changes in Net Assets or Fund Balances: Form 990, Part XI, line 5: Net unrealized losses on investments: -314. Donated services 32,575. Total to Form 990, Part XI, Line 5: 32,261.