1985: Peter St. George-Hyslop, a British neurologist and molecular geneticist, partners with Jean-François Foncin to isolate the genetic origins of Alzheimer’s disease in Family N.
1986: Dmitry Goldgaber, a Russian-born scientist working at the NIH, discovers the first-known mutation that causes Alzheimer’s. Known as the APP gene, it is located on chromosome 21, right where George Glenner predicted it would be. But it accounts for only a small fraction of the people who are inheriting Alzheimer’s disease through a genetic mutation.
1989: Leonard Heston at the University of Minnesota contributes to a brain autopsy of Galen “Moe” DeMoe. His collaborator, a nurse named June White, collects DNA from several DeMoe family members for Heston’s research exploring the possibility of a mutation different from the APP mutation located by Dmitry Goldgaber.
1990s
1992: Heston and White collaborate with biochemist Jerry Schellenberg at the University of Washington. Schellenberg narrows the search for a new mutation down to a segment of chromosome 14. The results are published in Science magazine.
1992: Lopera teams up with Harvard neuroscientist Ken Kosik to pursue research with the extended Colombian family and seek a cure.
1992: Allen Roses at Duke University identifies variations, which are called alleles, of the ApoE gene on chromosome 19 that heighten the risk of Alzheimer’s disease within the general population. Roses becomes convinced that the tau protein, not amyloid beta, is the chief culprit behind Alzheimer’s disease.
1995: St. George-Hyslop discovers a second mutation, which he names presenilin 1 (PS1), on the section of chromosome 14 previously identified by Schellenberg. PS1 turns out to be the most common genetic mutation in Alzheimer’s disease, afflicting the DeMoes and Family N, as well as Alois Alzheimer’s original patient, Auguste Deter.
1995: Schellenberg and others, including Rudolph Tanzi at Harvard, discover a third mutation—presenilin 2 (PS2)—on chromosome 1.
2000s
2002: After years of failed experiments, Bill Klunk, a psychiatrist, and radiochemist Chet Mathis—both at the University of Pittsburgh—develop a chemical known as “Pittsburgh Compound B,” or PiB, which allows science to view the progression of Alzheimer’s disease in a living brain for the first time, a critical tool in testing drugs that fight amyloid beta.
2006: Eric Reiman, a brain imaging expert and neuroscientist, partners with Pierre Tariot, a psychiatrist specializing in the design of clinical trials, to create an ambitious program through the Banner Alzheimer’s Institute in Phoenix to detect and attack Alzheimer’s in its earliest stages, before a person develops symptoms.
2006: Pearson “Trey” Sunderland III, chief of geriatric psychiatry at the National Institute of Mental Health, pleads guilty to criminal conflict of interest for his relationship with pharmaceutical giant Pfizer. His research, which includes samples drawn from members of the DeMoe family, is put on hold. The DeMoes transfer their efforts to the University of Pittsburgh, where they meet Klunk, who begins imaging their brains.
2008: John Morris at Washington University launches an international study of people who carry the known mutations causing Alzheimer’s disease. Through Klunk, the DeMoes enroll in Morris’s study, known as the Dominantly Inherited Alzheimer’s Network (DIAN). The study names neurologist Randy Bateman to lead its planned drug-trial unit.
2010: Reiman and Tariot establish a formal collaboration with Lopera and Kosik to test an anti-amyloid prevention drug for Alzheimer’s in the Colombian families identified by Lopera.
2012: The Obama administration sets a goal of finding a way to prevent and treat Alzheimer’s disease by 2025.
2012: DIAN’s trial unit begins testing two anti-amyloid drugs in people with an inherited genetic mutation, including members of the DeMoe family.
2014: Harvard neurologist Reisa Sperling and her longtime collaborator, Paul Aisen at the University of Southern California, launch a study testing one of the DIAN trial’s anti-amyloid drugs in people from the general population who are sixty-five to eighty-five years old. The study, known as A4, will also scan participants for the tau protein in hopes of one day adding an anti-tau drug to the trial.
2015: The DIAN trial begins scanning participants’ brains for the presence of the tau protein, which some researchers believe is more critical to the progression of Alzheimer’s symptoms than amyloid. Dean DeMoe is the first person scanned.
2015: The Alzheimer’s Association awards $10 million in new research funding to a trial launched by Reiman, Tariot, and the Banner Alzheimer’s Institute’s Jessica Langbaum testing two additional drugs in people ages sixty to seventy-five who carry two copies of the ApoE4 gene variant discovered by Roses in 1992. The study also plans to image participants’ brains for the tau protein, as does the study focusing on the Colombian family.
2015: Reiman, Tariot, Langbaum, Lopera, Bateman, Morris, Sperling, Aisen, and Roses are coauthors on a paper describing the Collaboration for Alzheimer’s Prevention, an initiative that allows them to share information gathered in their respective trials.
2025: The US target date for discovering a prevention and treatment of Alzheimer’s disease.
2050: Projected number of Americans with Alzheimer’s if a cure is not found: 13.8 million. Projected number worldwide: 131.5 million.
ABOUT THE AUTHOR
© REBECCA THURNER BRADDOCK
NIKI KAPSAMBELIS’s work has appeared in publications around the world, including the Washington Post, Los Angeles Times, People, and the Associated Press. She lives in Pennsylvania.The Inheritance is her first book.
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Notes
ONE: THE ENEMY WITHIN
In the United States, Alzheimer’s is the sixth-leading cause of death: “2016 Alzheimer’s Disease Facts and Figures,” Alzheimer’s Association.
Next to cancer, there is no condition more feared: Harris poll for MetLife Foundation, September 2010.
An estimated 24 to 36 million people worldwide—5.3 million in the United States alone: Martin Prince et al., “World Alzheimer’s Report 2015: The Global Impact of Dementia,” Alzheimer’s Disease International, reports that more than 46 million people worldwide have dementia. The report “2016 Alzheimer’s Disease Facts and Figures,” produced by the Alzheimer’s Association, estimates that 60 to 80 percent of all dementia cases are caused by Alzheimer’s disease.
Only one in four people who have the disease are actually diagnosed: “The World Alzheimer Report 2011,” Alzheimer’s Disease International.
Once thought to be relatively rare: “Understanding Alzheimer’s,” United Healthcare; “2016 Alzheimer’s Disease Facts and Figures.” Alzheimer’s Association.
Alzheimer’s is now known to be the leading cause of age-related dementia: Ibid.
The disease was first identified in 1906 by its namesake, Alois Alzheimer: Sources used for the story of Alois Alzheimer and his patient, Auguste Deter, include: Konrad Maurer and Ulrike Maurer, Alzheimer: The Life of a Physician & The Carrier of a Disease, translated by Neil Levi with Alistair Burns (New York: Columbia University Press, 1998); David Shenk, The Forgetting: Alzheimer’s: Portrait of an Epidemic (New York: Doubleday, 2001); Peter J. Whitehouse with Daniel George, The Myth of Alzheimer’s: What You Aren’t Being Told About Today’s Most Dreaded Diagnosis (New York: St. Martin’s Press, 2008); Márcio Borges, “A História de Auguste Deter,” Cuidar de Idosis, June 24, 2011; Hanns Hippius and Gabriele Neundörfer, “The Discovery of Alzheimer’s Disease,” Dialogues in Clinical Neuros
cience, March 2003.
In the second century, Roman emperor Marcus Aurelius: “Greek Medicine,” History of Medicine Division, National Library of Medicine, National Institutes of Health, first published September 16, 2002.
Doctors relied on clinical tests: “2016 Alzheimer’s Disease Facts and Figures,” Alzheimer’s Association, p. 14.
A study of 852 men diagnosed with Alzheimer’s disease: Robin Erb, “Diagnosis of Alzheimer’s Isn’t Always Accurate,” Detroit Free Press, May 17, 2012; “Experts Are Concerned About Misdiagnosis Rate for Alzheimer’s Disease,” McKnight’s, May 18, 2012.
Only about 1 percent of all Alzheimer’s patients: “2016 Alzheimer’s Disease Facts and Figures,” Alzheimer’s Association, p. 10.
their average age of onset is between thirty and fifty years old: “Younger/Early Onset Alzheimer’s & Dementia,” Alzheimer’s Association.
had invented a method for staining brain cells: David Shenk, “The Memory Hole,” New York Times, November 3, 2006.
“I have lost myself”: Ibid.
He attributed their dementia to atherosclerosis: Maurer and Maurer, Alzheimer: The Life of a Physician, p. 17.
Ironically, Kraepelin—who valued classification—unwittingly worsened a key confusion: Jesse F. Ballenger, “Progress in the History of Alzheimer’s Disease: The Importance of Context,” Alzheimer’s Disease: A Century of Scientific and Clinical Research, edited by George Perry, Jesus Avila, June Kinoshita, and Mark A. Smith (Amsterdam: IOS Press, 2006), p. 7; José Manuel Martinez Lage, “100 Years of Alzheimer’s Disease (1906–2006),” Alzheimer’s Disease: A Century of Scientific and Clinical Research, pp. 19–20.
Alzheimer himself didn’t dispute this: Ballenger, “Progress in the History,” p. 7.
were added to blue cardboard files and left to collect dust deep within Johann Wolfgang Goethe Frankfurt University Hospital: Whitehouse, The Myth of Alzheimer’s, p. 78.
TWO: THE SALT OF THE EARTH
Excerpts of letters from Galen DeMoe used with the permission of Gail DeMoe.
“It’s funny how at that age, sparks can fly”: Author’s interview with Gail DeMoe, August 24, 2011.
The self-proclaimed “oil capital of North Dakota,” Tioga lies nestled in the state’s northwest corner: “History of Tioga,” www.tiogand.net.
the Amerada Petroleum Corporation discovered oil in Tioga: Details about the Bakken Formation and the history of the oil industry in the region were drawn from “The Bakken Boom: An Introduction to North Dakota’s Shale Oil,” Energy Policy Research Foundation, Inc., August 3, 2011; “Son of Bakken Formation Namesake Remains Reserved,” Associated Press, December 3, 2012; and James Vlahos, “Oil Boom: North Dakota is the Next Hub of U.S. Energy,” Popular Mechanics, June 13, 2012.
“As far as Moe goes”: Author’s interview with Hank Lautenschlager, July 2012.
He and his best friend, Gary Anderson: Author’s interview with Gary Anderson, October 20, 2015.
“She drove this old car”: Author’s interview with Karla Hornstein, August 17, 2011.
One officer, who also happened to be Doug’s boxing coach: Author’s interview with Gary Anderson.
Gail herself had seen other changes: Author’s interview with Gail DeMoe.
To avoid parallel parking: Details of Wanda DeMoe’s illness were drawn from the author’s interviews with Gail DeMoe, February 14, 2013; Victor DeMoe, September 13, 2012; and Rob Miller, March 31, 2014.
Whatever was ailing Wanda also seemed to be affecting her two brothers: Author’s interview with Gail DeMoe, February 14, 2013.
When Wanda’s husband took her to a doctor, she was prescribed shock treatments: Ibid.
Bedsores covered her hips, buttocks, and shoulders: Autopsy report of Ruth (Wanda) DeMoe, Sacred Heart Hospital, Eau Claire, Wisconsin; autopsy no. 44668, July 15, 1964.
And in 1963, the year before she died, a group of doctors led by Robert Feldman: R. G. Feldman et al., “Familial Alzheimer’s Disease,” Neurology 13, no. 10 (1963).
Jerry adapted quickly to his oldest brother’s household: Author’s interview with Karla Hornstein, February 11, 2015.
Kindhearted neighbors took in Moe’s youngest brother, Ray: Ibid.
On March 25, 1967, Ray’s platoon was pinned down by enemy fire: “Elk Mound Marine Killed in Vietnam,” Eau Claire Leader, March 30, 1967.
At work, Hank Lautenschlager was slow to notice any changes: Author’s interview with Hank Lautenschlager.
Eventually, in 1974, Moe was let go from the job: Comprehensive History and Record Review of Galen DeMoe by the St. Cloud VA Medical Center, St. Cloud, Minnesota, July 16, 1981.
Karla, ever conscious of appearances, was so ashamed: Author’s interview with Karla Hornstein, February 11, 2015.
In the early Sunday morning hours of a summer heat wave: Letter from Lori DeMoe to Steve McIntyre.
“You’re just trying to make it through it all yourself”: Author’s interview with Karla Hornstein, February 11, 2015.
In August 1978: Details of Moe’s last night at home were drawn from the author’s interviews with Karla Hornstein, Dean DeMoe, Gail DeMoe, and Hank Lautenschlager.
THREE: FAMILY N
Things began to change in 1948: Daniel A. Pollen, Hannah’s Heirs: The Quest for the Genetic Origins of Alzheimer’s Disease (New York: Oxford University Press, 1993), pp. 55–59.
including the one written by Harvard’s Robert Feldman in 1963: Pollen, Hannah’s Heirs, pp. 143–144; Feldman et al., “Familial Alzheimer’s Disease.”
But the turning point came in 1968: Gary Blessed, Bernard Tomlinson, and Martin Roth, “The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects,” British Journal of Psychiatry, July 1968; Kenneth S. Kosik and Ellen Clegg, The Alzheimer’s Solution: How Today’s Care Is Failing Millions and How We Can Do Better (New York: Prometheus Books, 2010), p. 88.
It was into this beautiful, sometimes brutal land that French neuropathologist Jean-François Foncin landed in May 1973: Jean-François Foncin, “A Neuropathologist and Alzheimer Genetics,” Alzheimer: 100 Years and Beyond, edited by George Perry, Jesus Avila, June Kinoshita, and Mark A. Smith (New York: Springer, 2006), pp. 225–230.
such was reportedly the case with Feldman: Rudolph E. Tanzi and Ann B. Parson, Decoding Darkness: The Search for the Genetic Causes of Alzheimer’s Disease (Cambridge: Perseus, 2000), pp. 58–59.
Feldman did the best he could to analyze the family’s heredity with mid-1960s technology, but it wasn’t enough: Pollen, Hannah’s Heirs, p. 144.
Their 1985 paper appeared to offer: Ibid.
Hyslop found write-ups of a Canadian family: Author’s interview with Peter St. George-Hyslop, April 4, 2013; Pollen, Hannah’s Heirs, pp. 142–143,
The same committee members who had cut his grant nine years earlier: Foncin, “A Neuropathologist and Alzheimer Genetics,” p. 228.
FOUR: ONE IN A MILLION
Dr. Robert Katzman, a neurologist and medical activist from the University of San Diego: José Manuel Martínez Lage, “100 Years of Alzheimer’s disease (1906–2006), Journal of Alzheimer’s Disease 9 (2006) 15–26; H. Roger Segelken, “Robert Katzman, Alzheimer’s Activist, Dies at 82,” New York Times, September 23, 2008.
From 1980 to 1996, federal funding for Alzheimer’s research increased: Debra Kain, “Dr. Robert Katzman, Pioneering Alzheimer’s Disease Expert, Dies,” press release from the UC San Diego News Center, September 18, 2008.
Dmitry Goldgaber was up for the challenge: Biographical details about Dmitry Goldgaber drawn from the author’s interview with Dmitry Goldgaber, February 21, 2013; Dmitry Goldgaber, “My Story: The Discovery and Mapping of Chromosome 21 of the Alzheimer Amyloid Gene,” Journal of Alzheimer’s Disease 9 (2006) 349–360. Also appears in Alzheimer’s Disease: A Century of Scientific and Clinical Research, pp. 349–360 (see chap. 1, n. 16).
Gajdusek had built a career: Donald G. McNeil Jr., “D. Carleton Gajd
usek, Who Won Nobel for Work on Brain Disease, Is Dead at 85,” New York Times, December 15, 2008.
Goldgaber was ecstatic: Author’s interview with Dmitry Goldgaber.
Carleton Gajdusek wondered if Alzheimer’s: Goldgaber, “My Story.”
Prions are protein particles: Descriptions of prion disease aided by the “prion disease” entry in the Genetics Home Reference (National Library of Medicine, January 2014); Jim Schnabel, “Alzheimer’s Disease: Return of the Prion Hypothesis,” The Dana Foundation, February 17, 2012.
In 1980, Gajdusek tested the theory: McNeil, “D. Carleton Gajdusek.”
In 1984, a pathologist named George Glenner: Wolfgang Saxon, “Dr. George G. Glenner, 67, Dies; Researched Alzheimer’s Disease,” New York Times, July 14, 1995; Kosik and Clegg, The Alzheimer’s Solution, pp. 90–92.
He found them to be much smaller: Schnabel, “Alzheimer’s Disease: Return of the Prion Hypothesis.”
Virtually all people with Down syndrome: “Down Syndrome and Alzheimer’s Disease,” Alzheimer’s Association, 2015.
But back in the early 1980s, there was no database to search: Kosik and Clegg, The Alzheimer’s Solution, p. 91.
Gajdusek liked to excite them with scientific conundrums: Author’s interview with Dmitry Goldgaber.
Had he known, Goldgaber never would have bothered: Ibid.; Goldgaber, “My Story.”
When the amyloid precursor protein (APP) gene is mutated: Genetics Home Reference.
Goldgaber showed up and, after some negotiation, was allowed to pre-empt the program: Goldgaber, “My Story”; Tanzi and Parson, Decoding Darkness, pp. 79–81; Kosik and Clegg, The Alzheimer’s Solution, p. 92.
FIVE: YOU ARE MY SUNSHINE
“I remember asking my mother”: Author’s interview with Gail DeMoe, July 2012.
The Inheritance Page 31