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Robert Kolker tells the true story of a sprawling American family devastated by an inherited form of frontotemporal dementia (FTD), a rare neurodegenerative disease that attacks personality, judgment, and social cognition rather than memory. Woven through the family's multigenerational saga is a parallel history of neuroscience's struggle to understand the brain, from the 1848 case of Phineas Gage through the ongoing race to develop therapies that could one day eliminate FTD and open a pathway to treating Alzheimer's disease.
The family begins with Ollie and Jean, who married in 1950 and raised nine children across relocations from St. Louis to Canton, Ohio, to Pleasant Hills, Pennsylvania. Their marriage was strained by Ollie's infidelities, but Jean, a devout Catholic, refused to let him leave. Through the 1970s and 1980s, Jean withdrew from family life, drank heavily, and became emotionally absent. In 1988, the eighth child, Jenny, organized an intervention for Jean's drinking. Jean quit but never recovered. She died in 1990 of breast cancer she had kept hidden, at age 62. The youngest child, Barb, born in 1976, spent much of her childhood essentially alone with her deteriorating mother.
The first sibling to show unmistakable signs of illness was Christy, the second-born. After losing her pharmaceutical-company job in her late thirties, Christy stopped working, withdrew from her marriage, and neglected her children. Her husband filed for divorce in 1995, and by early 1996 police found her amid squalor. Doctors at New York Hospital diagnosed Pick's disease, a form of dementia. Sue, the third sibling, moved in with Christy and became her full-time caregiver, a role she would maintain for nearly three decades.
Kolker interleaves the family narrative with the history of brain science, beginning with the 1848 case of Phineas Gage, whose personality reportedly changed after an iron rod pierced his frontal lobe. He traces the early-20th-century discovery of Alzheimer's disease and Pick's disease, explains how Freudian psychoanalysis sidelined neurological explanations for decades, and describes neurologist Robert Katzman's 1976 campaign to rebrand senility as Alzheimer's disease. This campaign triggered a massive funding boom focused on beta-amyloid, a protein found in Alzheimer's plaques, marginalizing scientists who believed a different protein, tau, was equally important.
In the late 1990s, three independent research teams linked certain hereditary dementias to mutations in the MAPT gene, which produces tau. One team, led by neurogeneticist Tom Bird at the University of Washington, identified a specific mutation called V337M in a multigenerational family with early-onset behavioral dementia. The tangles this mutation produced were indistinguishable from Alzheimer's tangles, suggesting that a cure for V337M could serve as a back door to treating Alzheimer's.
Meanwhile, Barb joined the Peace Corps in 1998 and met her future husband Dave. In 2001, genetics counselor Jill Goldman collected DNA samples from several siblings, but the lab failed to identify a hereditary link, and the family assumed they were in the clear. That assumption collapsed in 2006 when Mary, the fifth sibling, arrived at Barb's Denver home displaying childlike speech and a lack of social awareness. Mary's husband Fred confirmed she had stopped working, showering, and bonding with their young son Mohammed. Barb realized for the first time that the illness was genetic.
A letter from a distant relative named Debbie, who had married into a California branch of the family, led to the discovery that the family's maternal great-grandfather had been institutionalized. In 2008, all nine siblings traveled to the Mayo Clinic, where researcher Brad Boeve diagnosed Mary with early-stage frontal-lobe degeneration. When Debbie's mother-in-law Elayne died shortly afterward and her brain tissue was donated, the Mayo Clinic confirmed she had carried V337M. Each sibling now had access to a definitive test, but many refused.
Kolker profiles Bruce Miller, the longtime director of the Memory and Aging Center at the University of California, San Francisco (UCSF), who became the field's leading authority on FTD. Miller's team maps behavioral changes to specific brain regions, finding that patients with right-frontal dysfunction lose the ability to recognize changes in themselves. Research by Miller's group and Berkeley psychologist Robert Levenson shows that FTD patients lose the capacity for embarrassment, shame, and empathy early, because these emotions depend on social cognition. Bill Seeley, a neuroscientist mentored by Miller, discovers that FTD patients lose most of their von Economo neurons, specialized cells supporting social functioning, and identifies the brain's salience network, which determines what information matters.
The disease claimed sibling after sibling. Jenny tested positive in January 2009. Over the following years she began hiding beer bottles and eventually had an affair, all while insisting she was fine. Her husband Bill spent years in denial before accepting his caretaking role. Peggy, the sixth sibling, tested positive in 2015, insisted she was asymptomatic, and was fired from her school-district job. Tim, a high school boyfriend, reconnected with her and became her devoted partner. Dutch, the fourth sibling, also tested positive in 2015. His truck-driving career ended after repeated accidents, and he disappeared for 18 months before turning up in a St. Louis hospital with a skull fracture. Sue cared for Christy throughout.
Barb spent a decade unable to face her own test. She created a daily symptom chart and contemplated suicide, but Dave told her that losing her would only bring more sorrow. She secretly submitted a sample at the Mayo Clinic without telling Dave, then discarded the notification that her results were ready. A year later, on September 23, 2017, she opened a thick envelope from a geneticist who had broken protocol to mail the news: Barb was negative. She and Dave wept with relief, but Barb felt immediate guilt toward the siblings who were not spared.
Kolker follows the next generation as they face the same fifty-fifty odds. Christy's daughter Cynthia tested positive at 30 and became pregnant naturally after four failed attempts at selective embryo transfer, an IVF procedure that screens embryos for mutations before implantation. Peggy's son Ansel tested positive at 23 and got a vasectomy to ensure the mutation would stop with him. Jenny's daughter Annika tested positive in February 2025. When she told Jenny, her mother insisted Annika must be negative, then showed tears, a rare emotional response. Mary's son Mohammed, raised by his father Fred in Omaha, learned of his risk in early 2025, years after Fred died. Four of five tested members of the next generation carried the mutation.
In the book's final movement, Kolker tracks the scientific and advocacy efforts converging around tau. He profiles Claire Clelland at UCSF, who runs the only lab developing a treatment for FTD using CRISPR, a technology for making targeted edits to DNA. Barb founded an advocacy group that later merged into Cure MAPT FTD, pushing pharmaceutical companies to test tau-targeting drugs on FTD patients. In 2025, UCSF obtained clearance to test an antisense oligonucleotide (ASO) treatment targeting excess tau in tauopathies, or tau-related neurodegenerative diseases, including MAPT-related FTD. The book closes with present-day scenes. Kathy, the eldest sibling, visits Dutch in assisted living; he does not recognize her. Kolker visits Sue and Christy in their small house near Pleasant Hills. Christy, now in her early seventies, barely speaks but still smiles. Sue has discovered breast cancer on Christy's right breast, just like their mother, and has chosen against aggressive treatment. An epilogue returns to a family videotape from 1997, when the siblings gathered on the Fourth of July, telling stories and lighting sparklers in the dark.
The family begins with Ollie and Jean, who married in 1950 and raised nine children across relocations from St. Louis to Canton, Ohio, to Pleasant Hills, Pennsylvania. Their marriage was strained by Ollie's infidelities, but Jean, a devout Catholic, refused to let him leave. Through the 1970s and 1980s, Jean withdrew from family life, drank heavily, and became emotionally absent. In 1988, the eighth child, Jenny, organized an intervention for Jean's drinking. Jean quit but never recovered. She died in 1990 of breast cancer she had kept hidden, at age 62. The youngest child, Barb, born in 1976, spent much of her childhood essentially alone with her deteriorating mother.
The first sibling to show unmistakable signs of illness was Christy, the second-born. After losing her pharmaceutical-company job in her late thirties, Christy stopped working, withdrew from her marriage, and neglected her children. Her husband filed for divorce in 1995, and by early 1996 police found her amid squalor. Doctors at New York Hospital diagnosed Pick's disease, a form of dementia. Sue, the third sibling, moved in with Christy and became her full-time caregiver, a role she would maintain for nearly three decades.
Kolker interleaves the family narrative with the history of brain science, beginning with the 1848 case of Phineas Gage, whose personality reportedly changed after an iron rod pierced his frontal lobe. He traces the early-20th-century discovery of Alzheimer's disease and Pick's disease, explains how Freudian psychoanalysis sidelined neurological explanations for decades, and describes neurologist Robert Katzman's 1976 campaign to rebrand senility as Alzheimer's disease. This campaign triggered a massive funding boom focused on beta-amyloid, a protein found in Alzheimer's plaques, marginalizing scientists who believed a different protein, tau, was equally important.
In the late 1990s, three independent research teams linked certain hereditary dementias to mutations in the MAPT gene, which produces tau. One team, led by neurogeneticist Tom Bird at the University of Washington, identified a specific mutation called V337M in a multigenerational family with early-onset behavioral dementia. The tangles this mutation produced were indistinguishable from Alzheimer's tangles, suggesting that a cure for V337M could serve as a back door to treating Alzheimer's.
Meanwhile, Barb joined the Peace Corps in 1998 and met her future husband Dave. In 2001, genetics counselor Jill Goldman collected DNA samples from several siblings, but the lab failed to identify a hereditary link, and the family assumed they were in the clear. That assumption collapsed in 2006 when Mary, the fifth sibling, arrived at Barb's Denver home displaying childlike speech and a lack of social awareness. Mary's husband Fred confirmed she had stopped working, showering, and bonding with their young son Mohammed. Barb realized for the first time that the illness was genetic.
A letter from a distant relative named Debbie, who had married into a California branch of the family, led to the discovery that the family's maternal great-grandfather had been institutionalized. In 2008, all nine siblings traveled to the Mayo Clinic, where researcher Brad Boeve diagnosed Mary with early-stage frontal-lobe degeneration. When Debbie's mother-in-law Elayne died shortly afterward and her brain tissue was donated, the Mayo Clinic confirmed she had carried V337M. Each sibling now had access to a definitive test, but many refused.
Kolker profiles Bruce Miller, the longtime director of the Memory and Aging Center at the University of California, San Francisco (UCSF), who became the field's leading authority on FTD. Miller's team maps behavioral changes to specific brain regions, finding that patients with right-frontal dysfunction lose the ability to recognize changes in themselves. Research by Miller's group and Berkeley psychologist Robert Levenson shows that FTD patients lose the capacity for embarrassment, shame, and empathy early, because these emotions depend on social cognition. Bill Seeley, a neuroscientist mentored by Miller, discovers that FTD patients lose most of their von Economo neurons, specialized cells supporting social functioning, and identifies the brain's salience network, which determines what information matters.
The disease claimed sibling after sibling. Jenny tested positive in January 2009. Over the following years she began hiding beer bottles and eventually had an affair, all while insisting she was fine. Her husband Bill spent years in denial before accepting his caretaking role. Peggy, the sixth sibling, tested positive in 2015, insisted she was asymptomatic, and was fired from her school-district job. Tim, a high school boyfriend, reconnected with her and became her devoted partner. Dutch, the fourth sibling, also tested positive in 2015. His truck-driving career ended after repeated accidents, and he disappeared for 18 months before turning up in a St. Louis hospital with a skull fracture. Sue cared for Christy throughout.
Barb spent a decade unable to face her own test. She created a daily symptom chart and contemplated suicide, but Dave told her that losing her would only bring more sorrow. She secretly submitted a sample at the Mayo Clinic without telling Dave, then discarded the notification that her results were ready. A year later, on September 23, 2017, she opened a thick envelope from a geneticist who had broken protocol to mail the news: Barb was negative. She and Dave wept with relief, but Barb felt immediate guilt toward the siblings who were not spared.
Kolker follows the next generation as they face the same fifty-fifty odds. Christy's daughter Cynthia tested positive at 30 and became pregnant naturally after four failed attempts at selective embryo transfer, an IVF procedure that screens embryos for mutations before implantation. Peggy's son Ansel tested positive at 23 and got a vasectomy to ensure the mutation would stop with him. Jenny's daughter Annika tested positive in February 2025. When she told Jenny, her mother insisted Annika must be negative, then showed tears, a rare emotional response. Mary's son Mohammed, raised by his father Fred in Omaha, learned of his risk in early 2025, years after Fred died. Four of five tested members of the next generation carried the mutation.
In the book's final movement, Kolker tracks the scientific and advocacy efforts converging around tau. He profiles Claire Clelland at UCSF, who runs the only lab developing a treatment for FTD using CRISPR, a technology for making targeted edits to DNA. Barb founded an advocacy group that later merged into Cure MAPT FTD, pushing pharmaceutical companies to test tau-targeting drugs on FTD patients. In 2025, UCSF obtained clearance to test an antisense oligonucleotide (ASO) treatment targeting excess tau in tauopathies, or tau-related neurodegenerative diseases, including MAPT-related FTD. The book closes with present-day scenes. Kathy, the eldest sibling, visits Dutch in assisted living; he does not recognize her. Kolker visits Sue and Christy in their small house near Pleasant Hills. Christy, now in her early seventies, barely speaks but still smiles. Sue has discovered breast cancer on Christy's right breast, just like their mother, and has chosen against aggressive treatment. An epilogue returns to a family videotape from 1997, when the siblings gathered on the Fourth of July, telling stories and lighting sparklers in the dark.
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By Robert Kolker
