The Inheritance

by Niki Kapsambelis

  Toward that end, some pharmaceutical companies—including Biogen and AC Immune, the company that created crenezumab, the anti-amyloid drug Banner was using in Colombia—continued developing drugs to target tau, opening the door to the possibility of eventually pursuing combination therapies that treated both plaques and tangles, the “holy grail” that Reisa Sperling had described.

  Aisen, though still a Baptist, was persuaded that tau was a worthy target. In 2015, the A4 study—like DIAN—began scanning patients’ brains for tau. Combined with the amyloid scans, it showed that tau levels continued to rise later in the disease, after amyloid had leveled off, and seemed to correlate more closely with the severity of the person’s symptoms.

  But Aisen said the scans also showed that tau levels, like amyloid, were rising before symptoms started, suggesting that when researchers did start offering anti-tau drugs, they should start early, and that anti-tau medication may be helpful throughout the disease, not just at the beginning.

  “I believe that the driver is amyloid, but that doesn’t mean amyloid is the best therapeutic target,” Aisen said. “I’ve placed my bet on amyloid. But until we’re successful, we have to pursue every plausible strategy.”

  Reiman recalled his dismay when he first heard the government set 2025 as the target date for finding a viable Alzheimer’s treatment. He feared that the field was risking its credibility: What if they didn’t meet that goal?

  But given the progress that had been made just in the past few years, he had changed his mind. Now he was gaining confidence that the trials were working. So many people had sacrificed so much to get there. Doctors had risked their careers. People like the DeMoes had bet their lives on it. When nobody cared about this disease, they had refused to fade away.

  “There is a strategic path forward,” Reiman said. “The stars are going to need to align, but we have a chance.”

  • • •

  As she learned about each new development in the field, Karla thought about how thrilled her mother would have been to see the progress that had been made in just the few years since her death.

  “To think, when she started, there was just nothing,” Karla said. “She would be so, so proud of the kids and the grandkids that are participating.”

  Deep in her heart, she hoped Gail was proud of her, too, and of her efforts to save her siblings, her nieces and nephews, her cousins. Once, she was the girl who refused even to go to the grocery store for her mother; now she had taken up Gail’s mantle. She wondered what her father would think of her.

  “Growing up with somebody with the disease, I was really dependent on other people. I needed my friends, needed Matt. And now I feel I can do this thing,” Karla said. “I guess since I’ve done it without Mom now, I feel like I can do it. We can go the distance. There’s so much progress, there is so much hope.”

  In the photographs, the notes, the home movies, and the memories she left behind, Gail loomed large in the lives of all she touched, emboldening them to keep fighting. To a person, her family, in the moments when they paused long enough to feel her presence, imagined they could hear her signature line:

  I love you to the moon and back.

  Ruth “Wanda” Hubbard, Moe’s mother (bottom row, second from left), graduating high school in 1924.

  DEMOE FAMILY

  Galen “Moe” DeMoe, left, and his brother Vic. Moe would inherit the disease that plagued their mother; Vic did not.

  DEMOE FAMILY

  Galen DeMoe’s high-school graduation photo, Eau Claire, Wisconsin. He wrote frequently to Gail, whom he met while working in the oil fields of North Dakota during the summer.

  DEMOE FAMILY

  Gail Helming’s high-school graduation photo, 1953. She was the valedictorian of her class of six, and her romance with Moe was well underway.

  DEMOE FAMILY

  Gail, seated left, visited Moe’s family in Wisconsin. Wanda DeMoe, seated right, acted strangely—but Gail dismissed the odd behavior because she was so in love. Standing behind her is Moe’s young sister, Pat.

  DEMOE FAMILY

  Gail and Moe’s wedding shivaree, August 27, 1955.

  DEMOE FAMILY

  Moe and his oldest child, Brian. Gail would always remember how much Moe loved kids, but their own children grew up to remember him much differently.

  DEMOE FAMILY

  Doug, in an undated photo, pulling his little brother Dean in a wagon. The two boys were inseparable growing up and were always known around town as “Dougie and Deanie.”

  DEMOE FAMILY

  Jerry DeMoe in 1966, the year he graduated from Tioga High School. He went to live with his older brother’s family when their mother, Wanda, was committed for symptoms they later learned were caused by Alzheimer’s disease.

  SHARON DEMOE

  Sharon Bratton, Tioga High School graduation photo, 1966. She would marry Jerry DeMoe, her high-school sweetheart, two years later.

  SHARON DEMOE

  Jerry and Sharon DeMoe on their wedding day in 1968.

  SHARON DEMOE

  Moe’s sister, Pat, settled in rural Wisconsin with her husband, Rob Miller, and their three daughters. Pictured here in 1969, left to right: Colleen, age 5; Robin, age 6; and Dawn, age 7.

  REBECCA VORK

  Gail and Moe’s six children, roughly 1971. Left to right: Dean, Karla, Lori (holding Jamie), Doug, and Brian.

  DEMOE FAMILY

  February 1972: Moe with his sons Dean (standing) and Jamie. A year later, prompted by her growing concerns about his disorientation and forgetfulness, Gail would bring Moe to a neurologist.

  DEMOE FAMILY

  Gail visiting Moe at the VA hospital in St. Cloud, Minnesota, where he lived from 1978 to 1986. He asked for her and the children often and pleaded to come home.

  DEMOE FAMILY

  The DeMoe siblings, 1986. Back row, from left: Jamie, Doug, Dean, and Brian. Front row: Karla, Gail, and Lori. By now, most were starting families of their own. Though their father would die three years later from autosomal dominant Alzheimer’s disease, none of them realized the seriousness of their own risk.

  DEMOE FAMILY

  Jerry and Sharon DeMoe in an undated photo with their older daughter, Sherry. They also had a younger daughter, Sheryl. The family settled in Oklahoma, where Jerry taught diesel mechanics.

  SHARON DEMOE

  Lori and her daughters (left to right): Jessica, Robin, and Chelsey. They traveled around the country following her husband’s job with Union Pacific Railroad, even living in a bunk car for a while.

  JESSICA MCINTYRE

  Dean DeMoe and his cousin Colleen in 1999. Both were successful in business and shared a rule-breaking spirit.

  DEMOE FAMILY

  Jerry DeMoe in 2003 with Sharon still by his side. In the background is Colleen Miller, the youngest daughter of Jerry’s sister, Pat. At the end stages of his life, Sharon brought him home to care for him and put on a brave face. But privately, she was desperate. She found comfort in talking to Jerry’s sister-in-law, Gail, who knew what she was enduring.

  SHARON DEMOE

  The McIntyre family, November 2007. From left: Chelsey, Jessica, Lori, Steve, and Robin. Though her family believed otherwise, Lori was convinced that she had the Alzheimer’s mutation. Before her diagnosis, she met with her closest friends and made them promise to watch over her daughters when she no longer could.

  JESSICA MCINTYRE

  Chet Mathis (left) and Bill Klunk from the University of Pittsburgh, whose Pittsburgh Compound B allowed science to view the progression of Alzheimer’s in a living brain for the first time. Klunk would later play a critical role in linking the DeMoe family to research testing experimental prevention drugs, and family members consult him often for advice and counsel.

  RIC EVANS

  In the 1990s, Kenneth Kosik (left), then a Harvard neuroscientist, teamed up with Francisco Lopera (right), a neurologist from Colombia who discovered the largest known extended family who carry a genetic
mutation for Alzheimer’s disease. Between them is Lucía Madrigal, a member of Lopera’s research team. Together they worked tirelessly to convince the rest of the scientific community of the value this family represented for research.

  KENNETH KOSIK

  Pierre Tariot (left) and Eric Reiman of the Banner Alzheimer’s Institute in Phoenix. Their ambitious plan to detect and attack Alzheimer’s before a person develops symptoms led to a collaboration with Ken Kosik and Francisco Lopera to test a prevention drug in the Colombian families.

  BANNER ALZHEIMER’S INSTITUTE

  Dr. Randy Bateman, head of the clinical trials unit of the Dominantly Inherited Alzheimer’s Network (DIAN). This international effort is testing experimental Alzheimer’s prevention drugs in the DeMoes and other families who carry the rare autosomal dominant mutations that cause the disease.

  WASHINGTON UNIVERSITY

  Gail DeMoe surrounded by her grandchildren, circa 2005. Clockwise from top left: Jennifer (Doug’s daughter); Lindsey (Dean’s daughter); Yancey (Brian’s son); Kassie (Brian’s daughter); Jessica (Lori’s daughter); Robin (Lori’s daughter); Chelsey (Lori’s daughter); Amber (Karla’s daughter), holding McKenna (Dean’s daughter), and Tyler (Dean’s son).

  DEMOE FAMILY

  Jamie DeMoe and his daughter, Savannah.

  DEMOE FAMILY

  Brian and his daughter, Kassie, at her college graduation.

  DEMOE FAMILY

  Gail (top) with her children. Clockwise from top right: Doug, Karla, Dean, Lori, Jamie, and Brian.

  JONI SYVERSON

  Karla and Brian during the end stages of Brian’s fight with Alzheimer’s disease. She dedicated her life to giving meaning to her family’s generational ordeal.

  DEMOE FAMILY

  Dean visiting his best friend, Monte Olson, in Australia, spring 2015.

  DEBRA DEMOE

  The DeMoe family enjoyed a special connection with Bill Klunk, who often joined them for dinner when they came to the University of Pittsburgh to participate in Alzheimer’s research. Left to right: Dean; Karla’s daughter, Amber; Karla; Dean’s wife, Deb; and Dr. Klunk.

  DEBRA DEMOE

  Acknowledgments

  To allow a stranger complete access to the most intimate details of your family history requires a leap of faith that, in all honesty, I’m not certain I would have the courage to make. Yet that is exactly what the DeMoe family did for me, and without their trust, their story would have been impossible to tell. They showed me every bump and wrinkle, every triumph and defeat, and they welcomed me as their own. I can never repay them for that privilege. I can only hope that the end result, which not all of them survived to see, is worthy of that trust. You are paisa.

  To my agent, Larry Weissman, and his wife and business partner, Sascha Alper, thank you for believing in this story and championing it every step of the way. Thanks also to author Dave Kinney, my onetime AP colleague, for introducing me to Larry and sharing with me the process for pitching a book.

  Millicent Bennett was my first editor at Simon & Schuster, and I am indebted to her for shepherding this manuscript, pushing me beyond what I thought were my limits, and for caring about its characters as much as I do. Karyn Marcus, who became my second editor, helped me see the story through a new lens and bring it to fruition, culminating years of planning and research. Thank you, both.

  To the brilliant minds whose lives have been spent in pursuit of a single goal—to rid the world of Alzheimer’s—I am humbled by, and grateful for, your generosity in helping me tell this story. Bill Klunk, Chet Mathis, Snezana Ikonomovic, and the entire staff of the University of Pittsburgh’s Alzheimer’s Disease Research Center—thank you for the many hours we spent together. From the DIAN team, I would like to thank Eric McDade (first of Pitt, now of Washington University), Randy Bateman, and John Morris. From the Banner team, I thank Eric Reiman, Jessica Langbaum, and Pierre Tariot; their accessibility, even in the midst of this most important work, was both impressive and critical. Being able to relate such complex scientific information in an elegant way is a rare gift, and you have it. To Teresa Zyznewsky, I am grateful for your translation help, which allowed me to reach out to Dr. Lopera; to Francisco Lopera and Ken Kosik, I thank you for sharing your adventures with me, and I hope to one day join you. I thank Ken also for the many times you clarified and expanded upon your work and for your seemingly limitless patience. I thank Paul Aisen and Reisa Sperling of the A4 trial: With minds such as yours working on this problem, I can’t help but be filled with hope. I am grateful to June White, Peter St. George-Hyslop, and Jerry Schellenberg for their willingness to speak to me, and to Dmitry Goldgaber for sharing his remarkable story.

  I am indebted to Becky Vork and Monte Olsen, who helped me understand what true friendship means and restored my faith in its existence. Monte, thank you for the dance. I am grateful to Julie Noonan Lawson and Kate Preskenis for speaking to me about their family’s experiences.

  Writing can be a lonely occupation, but for the shared experiences of those who have been there before. Thank you to Fawn Fitter, who included me in her acknowledgments and to whom I am finally returning the favor; and to Cindi Lash and Chuck Finder, for their counsel and friendship. The best writers I ever knew were the journalists of the Associated Press in Concord, Los Angeles, and Pittsburgh. There are too many of you to name individually, but I thank you all the same for showing me the way.

  I am blessed with resourceful friends who were kind enough to help me with my research, particularly Stuart Culy, who tracked down congressional testimony, and Tina Wood, without whom I might never have found the elusive June White. Julian Neiser’s legal advice and assistance in locating documents related to Trey Sunderland were immensely helpful, and he’s also a talented journalist when he’s not busy practicing law.

  My friend Sam Menchyk was essential in uploading and, in many cases, restoring the photographs that illustrate this book. He has also been indispensable in advising me about the digital storytelling process as I develop the book’s website. I can never adequately thank him for his expertise and generosity.

  I thank my own family and friends: my father, George Kapsambelis, who made me believe I could do anything because he believed it; my mother, Leslie Kapsambelis, a writer who wanted me to follow in her footsteps and celebrated each step of that journey; and my grandmother and personal hero, Helen Kapsambelis, who taught me the lengths to which a parent will go to save her children. To my nuclear family: Dave Adler, who was integral to the logistics of this project and took care of my most precious assets, Bobby and Tim Adler, while I traveled.

  To Bobby and Tim: Simply stated, you are my reason for being. Nobody will ever be more important to me than you are.

  Last, I thank Craig Brickell, who always told me the truth and sat across the table from me one evening at a bar in Pittsburgh and told me I had to write this story.

  A Timeline of Discovery in Alzheimer’s Disease

  1900s

  1906: Alois Alzheimer, a German psychiatrist, identifies a new disease in a fifty-one-year-old woman named Auguste Deter. Alzheimer’s boss later names the disease after him.

  1940s

  1948: A London doctor named R. D. Newton reviews the previous forty years’ worth of literature and concludes that Alzheimer’s and old-age senility are the same disease. He also guesses that a hereditary pattern is at play.

  1960s

  1963: Neurologist Robert G. Feldman, first at Yale and later at Boston University, writes a paper about a family whose history with Alzheimer’s seems to suggest a pattern of genetic inheritance.

  1968: British scientists Gary Blessed, Bernard Tomlinson, and Martin Roth write a seminal paper concluding, once and for all, that dementia in older people is the same disease as Alzheimer’s in younger people. This is one of the first hints indicating how widespread the Alzheimer’s problem actually is.

  1970s

  1972: Jean-François Foncin, a French neuropathologist, diagnoses a young mot
her with Alzheimer’s. By tracing her ancestry, he discovers a large extended family who carry a mutation that causes Alzheimer’s disease. He later realizes they are the same family who formed the basis for Robert Feldman’s research. They come to be known in medical literature as “Family N.”

  1976: Robert Katzman, a neurologist and medical activist from the University of California San Diego, identifies Alzheimer’s disease as a “major killer” in an editorial he writes for the American Medical Association’s Archives of Neurology.

  1980s

  1980: Katzman helps found the Alzheimer’s Association. From 1980 to 1996, federal funding for Alzheimer’s research increases from $5 million to $300 million.

  1984: George Glenner, a pathologist from the University of California at San Diego, identifies the exact makeup of the protein that forms the amyloid plaques found in Alzheimer’s patients. Known as amyloid beta, they are fragments of a protein manufactured by chromosome 21, the same chromosome that is duplicated in people with Down syndrome.

  1984: Colombian neurologist Francisco Lopera meets his first patient suffering from genetically inherited Alzheimer’s disease. The patient turns out to be a member of the largest-known family tree of people with this form of the disease.