QUARTERLY REPORT: 4TH QUARTER 2014 Q4 2014

INSIDE THIS REPORT

‘,’ Still in Search of a Cure 2 Mini Film Festival Raises Driving Genes Funds to Fight Alzheimer’s to Therapies™ 3 Financial and Research Building on its enormously successful “Whole Genome Sequencing” Project, which Update identified nearly 1,000 new genetic mutations in more than 50 different genes, Cure 4 Alzheimer’s Fund has announced a new, even more ambitious multiyear, $50 million plus program titled “Genes to Therapies” (G2T). Simply put, the new project’s goal Cure Alzheimer’s Fund is to use the most promising recent genetic discoveries to develop drugs that would Heroes stop the disease at three separate stages: 5 ••For healthy people who don’t yet have Alzheimer’s: to stop Alzheimer’s before Global Family Reunion it starts by inhibiting the production of the Abeta protein and/or clearing it from the brain after it forms. 6 ••For those exhibiting symptoms of Alzheimer’s: to stop the process early on by Sherry Sharp Joins inhibiting the formation of tau tangles and protecting neurons from undue stress. Cure Alzheimer’s Fund Board ••For those whose disease has progressed significantly: to reduce the Abeta and 6 tau-provoked inflammation, slowing down or even stopping the disease process.

“This is indeed a major challenge,” said Research Consortium Chair Dr. Rudy Tanzi,

“but I believe we now have the data, the technology and the funding to take it on.” The first step, he explained, will be to prioritize approximately 15 genes that fit several key criteria: ••they must have a clear impact on Alzheimer’s pathology; Don’t Miss Our ••they must be “druggable”—connected to known biological systems, producing proteins similar to those already targeted by other drugs; and Upcoming Webinar ••they must impact one of the clear intervention points—Abeta/plaque Feb. 6 at 1 p.m. EST production, tangle formation or neuroinflammation.

G2T will be aided significantly by the recent “Alzheimer’s-in-a-dish” From Genes breakthrough by Tanzi and Dr. Doo Kim at Massachusetts General Hospital. Using stem cells, Dr. Kim was—for the first time—able to to Therapies create both the amyloid plaque and neurofibrillary tangle pathology Tune in live to the site of the Cure of AD in a Petri dish. This technology will enable much cheaper and Alzheimer’s Fund Research Consortium’s faster drug testing. annual meeting to hear the latest progress from our Genes to Therapies Steering “Having learned much about the pathway that leads to disease, Committee. The Alzstream™ webinar will together with the genes responsible,” said Tanzi, “we now can proceed be moderated by David Shenk, author to look for chemical compounds that correct the defects. In other words, of “The Forgetting,” and will feature each we can try to fix what is broken.” of the members of the G2T Steering continued on page 2 » Committee. No sign-up necessary. Log on at http://curealz.org/webinar. n

curealz.org continued from page 1 » Genes to Therapies (G2T) Steering Committee To ensure the success of the G2T program, Cure Alzheimer’s Fund is funding a unique research facilitation process—the “infrastructure” for the project. This involves recruiting researchers with Genes to Therapies expertise in specific genes and providing them with the specialty mice and reagents they will need to do their Alzheimer’s investigations relative to their particular genes. Unlike most projects, which require six to nine months’ preparation time before any real research begins, our unique approach will save money and, most importantly, time, allowing our researchers to get started right away.

Working as one, our G2T Steering Committee’s ultimate goal is to develop effective drug therapies at three different points in the pathological cascade of the disease to prevent, inhibit and cure Alzheimer’s. Here’s a quick look at each of the players.

Rudy Tanzi, Ph.D., Sangram S. Sisodia, David Michael Holtzman, Chairman, Cure Ph.D., Cure Alzheimer’s M.D., Cure Alzheimer’s Alzheimer’s Fund Fund Research Fund Research Consortium Research Consortium Consortium The Andrew B. and Gretchen P. Jones Joseph P. and Rose F. Kennedy Thomas A. Reynolds Sr. Family Professor of Neurology and Head Professor of Neurology at Harvard Professor of , of the Department of Neurology, University and Director of the Genetics and Aging University of Chicago Director, Washington University, St. Louis Research Unit at Massachusetts General Center for Molecular Neurobiology Like Sisodia, Dr. Holtzman has a background in Hospital (MGH) A longtime collaborator of Tanzi’s, Sisodia is a biology and has helped to identify the most effective Tanzi was the pioneering scientist who discovered leading expert on the molecular and cell biology of interventions from specific gene functional variants in the linkage between specific genes and Alzheimer’s Alzheimer’s disease pathology; he has been at the Alzheimer’s disease. Dr. Holtzman is involved in clinical disease. Today Tanzi leads the Alzheimer’s Genome forefront of learning how the familial Alzheimer’s and research activities at the Washington University Project™, a groundbreaking initiative dedicated to disease (FAD) genes, including the amyloid Memory and Aging Project and the Alzheimer’s Disease finding all the genes associated with Alzheimer’s precursor protein and the presenilins, function Research Center. He has contributed greatly to our disease so we not only can repair the damage the normally and contribute to Alzheimer’s disease understanding of how anti-amyloid antibodies affect disease has caused, but prevent it from occurring. pathogenesis. His role on the committee is to help Alzheimer’s pathology and how Abeta is cleared from Tanzi’s role as chair of the G2T Steering Committee is identify other researchers, beyond the Research the brains of Alzheimer’s patients. As a member of the to coordinate the efforts of the researchers as well as Consortium, who are more familiar with designated steering committee, he will assist in identifying other to continue his innovative research on what causes genes. Sisodia was very instrumental in designing researchers with similar skills to investigate how the Alzheimer’s disease and how it develops. and implementing the unique “infrastructure” to designated Alzheimer’s genes affect the pathology, and facilitate the more rapid and cost-effective research bring his clinical experience to bear in setting priorities program for Genes to Therapies. for potential drug development.

‘Still Alice,’ Still in Search of a Cure

The recently released highly acclaimed motion picture ‘Still Alice’ originated as a novel. The author, Lisa Genova of Cape Cod, Massachusetts, wrote the story of an Ivy League professor who is diagnosed with early-onset Alzheimer’s disease. As a who actually worked at Massachusetts General Hospital with Rudy Tanzi long before her book was published, Genova knows the complexity of the science behind the disease and the frustrations over the lack of cure. Now that “Still Alice” has become a bestseller, Genova has made a plea to her readers in a reprinting of her book to support Alzheimer’s research. To find out more, visit lisagenova.com/still-alice/. n

“Still Alice” author Lisa Genova

2 Steven Wagner, Ph.D., Wilma Wasco, Ph.D. Cure Alzheimer’s Fund Associate Professor of Neurology, Research Consortium Genetics and Aging Research Unit, Principal Investigator, Department of Massachusetts General Institute for Neurosciences, School of Medicine, Neurodegenerative Disease, of California, San Diego Medical School and Massachusetts General Hospital Wagner has an extensive background in biochemistry and drug discovery and has numerous Wasco was part of an international collaborative patents to his name. Along with Tanzi, he helped effort that identified the familial Alzheimer’s disease- “Thanks to our develop the first gamma-secretase inhibitor for associated presenilin 1 (PS1) and presenilin 2 Alzheimer’s disease, which later provided the (PS2) genes. Her research has evolved to focus on donors we’ve been platform for gamma-secretase modulators, which understanding the biological role certain AD-linked control amyloid production rather than stop it proteins play in the normal, aging and diseased able to embark on altogether. “If we administer this at the right time to brain. As research operations manager for the G2T ™ the right populations, it could help to slow down the project, Wasco will be responsible for facilitating the ambitious G2T disease process,” said Wagner. As a member of the communication among the various researchers, and project, which is steering committee, he will focus on genes that may managing and maintaining the core facilities and provide clues for early prevention. research materials, including specially engineered moving us closer laboratory mice. She also will develop and maintain Robert Vassar, Ph.D., a G2T publications resource and provide the to a cure.” operations management necessary for this complex Cure Alzheimer’s Fund —Tim Armour, president and CEO, and unique undertaking. Research Consortium Cure Alzheimer’s Fund Professor of Cell and Molecular Biology, Feinberg School of Tim Armour, President Medicine, Northwestern University and CEO, Cure Alzheimer’s Fund Vassar’s ongoing research focuses on the role of Abeta and the enzyme BACE1 in normal biological Armour brings an extensive processes and in disease mechanisms of relevance background in nonprofits and to Alzheimer’s disease. As a pioneer in Alzheimer’s fundraising to Cure Alzheimer’s research, Bob has made a number of discoveries Fund as well as an MBA from Harvard. Armour joined critical to progress in the field. As a member of Cure Alzheimer’s Fund 10 years ago to help lead the the Genes to Therapies Steering Committee, he charge in the quest for a cure. As the administrator will help ensure proper attention is paid in the G2T of the steering committee, Armour is responsible for research projects to the more basic aspects of how supporting the researchers, developing and securing Alzheimer’s-relevant genes are produced and how budgets, and being the liaison between the committee they affect the disease pathology. and the Cure Alzheimer’s Fund Board of Directors. n

In 2010 at age 59, longtime reporter “Living with Mini Film and writer Greg O’Brien of Brewster, Alzheimer’s” Massachusetts, was diagnosed with early- short films, an onset Alzheimer’s disease. O’Brien wrote early-release Festival the book “On Pluto: Inside the Mind of clip from Alzheimer’s” about his experience with “Still Alice” Raises Funds the disease, which David Shenk, author of and a panel “The Forgetting,” produced as a short film, discussion to Fight part of his four-film project “Living with about From left, Greg O’Brien, Alzheimer’s.” O’Brien and Lisa Genova, also Alzheimer’s Lisa Genova and David Shenk a Cape Cod, Massachusetts, native and featuring Greg Alzheimer’s author of “Still Alice,” are friends, along with O’Brien, novelist Lisa Genova and Cure Linda Apsey of Cape Cod. Apsey wanted Alzheimer’s Fund’s Mike Curren, which was to help promote O’Brien’s book and raise moderated by David Shenk. Apsey recruited money for Alzheimer’s research, so she dozens of sponsors and her efforts attracted organized a film festival and fundraiser 150 people; together they raised $12,000 in Chatham’s historic Orpheum Theater for Cure Alzheimer’s Fund. To view the short last November. The event featured the films, visitlivingwithalz.org . n

3 34 Washington St., Suite 200 Wellesley Hills, MA 02481 Financial Update Telephone: 877-CURE-ALZ (287-3259) This Quarter* YTD* Inception to Date Fax: 781-658-2399 curealz.org Fundraising $7,100,000 $10,764,000 $48,245,000 Centre City Tower 650 Smithfield St., Suite 2015 Pittsburgh, PA 15222 Expenses paid for by the founders $599,000 $1,780,000 $9,490,000 Telephone: 412-261-2785

Funded research $1,492,000 $5,359,000 $28,021,000 Mission Fund research with the highest probability of *Numbers shown are preliminary for the period and are rounded to the nearest $1,000. preventing, slowing or reversing Alzheimer’s disease. Research Consortium Develops and updates a “roadmap for research” for the most effective and efficient route to preventing, slowing Research Update or reversing Alzheimer’s disease. Members research their Research funded during the fourth quarter of 2014 own projects and recruit others whose work will hasten Distribution development of effective therapies for and prevention of Alzheimer’s disease. Project Researcher Amount Rudolph E. Tanzi, Ph.D., Chairman, Research Consortium; /Massachusetts General Hospital Alzheimer’s Genome Project™, Phase 3 Rudy Tanzi, Ph.D. $800,000 Sam Gandy, M.D., Ph.D., Icahn School of Medicine at Mount Sinai Mass General/Harvard University Charles Glabe, Ph.D., University of California, Irvine David Michael Holtzman, M.D., Washington University, St. Louis Air Pollution and APP Processing Caleb Finch, Ph.D. $90,908 Richard L. Huganir, Ph.D., The Johns Hopkins University University of Southern California Virginia M.-Y. Lee, Ph.D., M.B.A., University of Pennsylvania Roberto Malinow, M.D., Ph.D., University of California, San Diego Eric E. Schadt, Ph.D., Icahn School of Medicine at Mount Sinai G2T: The Role of TREML2 in Marco Colonna, M.D. $100,000 Sangram S. Sisodia, Ph.D., University of Chicago Alzheimer’s Disease** Washington University, St. Louis Robert Vassar, Ph.D., Northwestern University Steven L. Wagner, Ph.D., University of California, San Diego Development of an APP-Specific Lawrence Rajendran, Ph.D. $100,000 Berislav Zlokovic, M.D., Ph.D., University of Southern California β-Secretase Inhibitor for AD Therapy University of Zurich Scientific Advisory Board Reviews individual grant proposals for science integrity G2T: Centralized Research Core** Wilma Wasco, Ph.D. $91,150 and roadmap objectives. Provides advice and counsel to Massachusetts General Cure Alzheimer’s Fund regarding scientific soundness of the roadmap. G2T: Research Models and Materials** Taconic Biosciences Inc. $310,000 John C. Mazziotta, M.D., Ph.D., Chairman, Scientific Advisory Board; UCLA Dennis Choi, M.D., Ph.D., Stony Brook University Total Distributed to Research for Q4 2014 $1,492,058 Caleb Finch, Ph.D., University of Southern California Paul Greengard, Ph.D., The Rockefeller University **G2T: The Genes to Therapies™ project will determine how high-priority genes are involved John S. Lazo, Ph.D., University of Virginia in Alzheimer’s pathology and how that information can be used to facilitate more rapid development Robert C. Malenka, M.D., Ph.D., Stanford University of effective therapeutic interventions. William Mobley, M.D., Ph.D., University of California, San Diego Thomas C. Südhof, M.D., Stanford University Marc Tessier-Lavigne, Ph.D., The Rockefeller University Board of Directors Help us fund research with the highest probability Jeffrey L. Morby*, Key Largo, Fla., Chairman Robert F. Greenhill, New York City of preventing, slowing or reversing Alzheimer’s Henry F. McCance*, Lake Wales, Fla. Jacqueline C. Morby*, Key Largo, Fla. disease. Donations can be made through our Phyllis Rappaport*, Stuart, Fla. Sherry Sharp, Richmond, Va. website, www.curealz.org/donate, Matthew Szulik, Boston Tim Armour, Wellesley Hills, Mass., President or sent directly to our office. *Founder Administration For gifts of securities or direct wire transfers, please Tim Armour, President and CEO Mike Curren, Senior Vice President contact Tim Armour at 877-CURE-ALZ (287-3259) Sally Rosenfield, Senior Vice President David Shenk, Senior Adviser for further information. Laurel Lyle, Director of Fundraising Programs Toni Carbone, Office Manager Madeleine Adelson, Marketing Manager Cindy Turner, Accountant Jessica Mutch, Controller Dorothy Vacaro, Gift Processing and Finance Associate

CHARITY DESIGNATION Contributing Writer: Patty Bovie Cure Alzheimer’s Fund ® is a “doing business as” name for the Alzheimer’s Disease Research Copy Editor: Colleen O'Neill Foundation, a 501(c)(3) public charity with federal tax ID #52-2396428. Design: Winking Fish

4 CURE ALZHEIMER’S FUND HEROES

“Your donations make a big difference in our progress toward finding a cure for Alzheimer’s disease. Your passion, your energy and your generosity are an inspiration to all of us to work even harder to end this terrible disease. Thank you all for your leadership and support.” —Tim Armour, president and CEO, Cure Alzheimer’s Fund Robin and the guys from Express Oil Change Oil Change for a Cause GraceAdena.com Seven Robin and Gregg Gaskins both have a family Philadelphia artist and Stages of history of Alzheimer’s disease, having lost jewelry designer Nicole Alzheimer’s their mother and grandmother, respectively, D’Amico created and Toni Wombaker to the disease. They run a family business, named her online of Pahrump, Express Oil Change and Service Center boutique, GraceAdena. Nevada, has a in Columbia, South Carolina, and wanted com, for her background in to do something to help fight Alzheimer’s. grandmother, who has education and Toni and Yvonne For one month last fall, they donated $1 to had Alzheimer’s since Nicole D’Amico is a mother of Cure Alzheimer’s Fund for every oil change 2007. Nicole creates four. She also they did, and encouraged their customers and sells beautiful has cared for her mother, Yvonne Jensen, to donate as well, raising $4,600. They are custom jewelry not only 71, who has had Alzheimer’s disease since planning on making this an annual event. n to adorn women of all 2009. “When my mom came to live with ages, but also to us, I didn’t realize what this disease was Mom and raise awareness Forget really like, but it didn’t take long to learn,” for Alzheimer’s Me Not she said. After seeing Cure Alzheimer’s Son Run for Charms Memories disease. One Fund advocate Alan Arnette speak, Toni of Nicole’s was inspired to start video documenting her For the past collections, “Forget Me mom to educate others. Last October Toni two years, Kim Not,” was named as such held an event and showed her latest film, Chan, 44, of to honor her family’s fond “The Seven Stages of Alzheimer’s Through Huntington Beach, memories of Grace before she a Caregiver’s Eyes,” collecting more than California, has run became ill. “Although my grandmother $100 for Cure Alzheimer’s Fund. n the Long Beach is no longer able to reminisce with us, half-marathon we remember for her,” said Nicole. in honor of her Ethan and Kim A portion of each purchase will go to grandfather, who Cure Alzheimer’s Fund. n died from Alzheimer’s disease. This year, Kim’s 11-year-old son, Ethan Lam, ran along with her, beating her time by 20 SquallFest minutes. “He came in third in his age Music has group and raised more than $1,000 for always had Cure Alzheimer’s Fund. I’m so proud that the power to he was able to achieve a challenging heal, but Bryan personal goal and fundraise for a worthy Minks, 32, cause,” she said. n of Lexington, Quentin (in the purple) fighting Kentucky, A Champagne Birthday really brought ‘The Hero’ Katerina Sourgiadakis of that concept Quentin “The Hero” Henry, 25, of West Littleton, New Hampshire, 24 to life at Monroe, Louisiana, is an up-and-coming knew that celebrating her 24th SquallFest, an mixed martial arts fighter who supports a birthday on the 24th of September annual music different charity every time he fights. Last (her “champagne birthday”) needed to festival. This November, he wore purple shorts with the be something special. Her grandmother year Bryan, Musicians perform at Cure Alzheimer’s Fund logo on them for SquallFest passed away from Alzheimer’s disease a musician one of his fights—available for viewing in 40 two years before and Katerina wanted to himself, decided he wanted to add a million homes. “I have a platform where I can honor her grandmother as part of her own fundraising element to the event, and raise awareness for different causes, and it’s birthday celebration. Instead of asking donated a portion of all ticket proceeds my responsibility to do something good with for gifts, Katerina hosted a Wiffle Ball to Cure Alzheimer’s Fund in an effort to that platform,” said Quentin. “I help charities game and asked her friends and family to raise awareness for the cause. SquallFest by donating an advertising spot on my donate at least $5 to play. Together they was held last September with 100 people shorts for free. I always want to help people raised $550 for research. n in attendance. They raised $600. n who are struggling. This is my way.” n

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Global Sherry Sharp Joins Family Cure Alzheimer’s Fund Board

Reunion Sherry Sharp, 67, of Richmond, Virginia, was married to her high We are all connected in some way. That’s the premise of “The Global school sweetheart and founder of Family Reunion,” the largest family CarMax, Richard Sharp, for almost reunion in history to be held at the 46 years. Last June, he lost his New York Hall of Science, site of the 1964 World’s Fair. The event battle with Alzheimer’s disease. will include talks by celebrities, To honor her husband’s memory, Sharp scientists and comedians and fun recently joined Cure Alzheimer’s Fund’s family activities, and will raise money Board of Directors to help in the fight for Alzheimer’s. To find out more, for a cure. Sharp is director of the visit globalfamilyreunion.com. n investment firm V-Ten Capital Partners and a published author with the “Chicken Soup for the Soul, Alzheimer’s and Other Dementias” edition. Her story, “Life Interrupted,” was inspired by her experience as a caregiver to her husband after he was diagnosed with early-onset Alzheimer’s disease in 2010. Sharp brings tremendous passion, experience and years of philanthropic efforts to her new role. n

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