Standard preventive advice like daily crossword puzzles, 150 minutes of weekly exercise, and the Mediterranean diet lower dementia risk for most people, but for some individuals cognitive decline is driven entirely by DNA rather than lifestyle habits. In his new book, “The Vanishing Family: Love, Fate and the Quest to End Dementia,” author Robert Kolker examines a family facing this genetic reality, exploring how rare inherited forms of the condition may unlock broader treatments for age-related brain impairment.
Chronicle of a Genetic Mutation on Chromosome 17
The book centers on Barb, a 50-year-old woman born as the youngest of nine children in Pittsburgh to parents Ollie and Jean. While still living at home, Barb witnessed her mother Jean withdraw from the world in her 50s, spending days sitting before the television, smoking, and drinking while hiding a breast cancer diagnosis that ultimately led to her death at age 62. Years later, Barb’s second-oldest sister Christy, a successful 44-year-old executive with two children, experienced an eerily similar transformation as her marriage ended and she stopped taking care of herself or handling her job. Christy was eventually diagnosed with Pick’s disease, a form of frontotemporal dementia (FTD) occurring in people under 65.
After a third sister, Mary, began showing identical symptoms in her 40s—failing to communicate normally or recognize everyday courtesies—Barb and her surviving sisters pieced together clues and consulted experts. They discovered that a mutation on chromosome 17, known as V337M, causes a rare form of early-onset FTD in their family. Offspring of carriers face a 50/50 chance of inheriting the mutation, forcing each family member to decide whether to undergo predictive testing.
Did you know? While most cases of Pick’s disease are sporadic and not inherited, genetic mutations like V337M on chromosome 17 cause rare forms of early-onset frontotemporal dementia that affect multiple generations.
How Studying Rare Dementia Informs Alzheimer’s Research
For decades, medical researchers focused heavily on the “amyloid cascade hypothesis,” theorizing that accumulated amyloid plaques caused Alzheimer’s disease, despite continuous failures of plaque-clearing drugs in clinical trials. Robert Kolker explains in the book that this represented a period of scientific groupthink that largely ignored how abnormal changes in tau proteins contributed to cognitive decline. Scientists have only recently recognized that studying rarer, simpler forms of dementia like FTD can reveal critical mechanisms for treating broader age-related brain impairments, including Alzheimer’s.
The family’s V337M mutation causes normally helpful tau proteins to malfunction, negatively impacting behavior, personality, and cognitive function. According to Kolker’s reporting, tau-targeting drugs are currently in clinical testing phases, alongside exploration into gene therapy and gene editing to address specific mutations.
The Need for Patient Participation in Clinical Trials
Advocacy groups like the Association for Frontotemporal Degeneration have pushed for greater scientific attention toward the disease, but undercounting remains a significant barrier to research. Robert Kolker notes that doctors often avoid testing for incurable rare diseases because treatments do not yet exist, leaving the estimated 60,000 U.S. FTD cases largely undercounted. However, researchers and drug companies require active patient registries to justify the investment needed to find viable treatments.
Genetic causes and inheritance of Pick's disease and frontotemporal dementia
What causes frontotemporal dementia like Pick’s disease?
Most cases of Pick’s disease are sporadic, meaning they occur without an inherited link. However, certain rare forms are caused by specific genetic mutations, such as the V337M mutation on chromosome 17 identified in Kolker’s book.
How is the V337M mutation inherited?
Offspring of individuals carrying the V337M mutation on chromosome 17 have a 50/50 chance of inheriting the genetic trait themselves.
Why are rare dementia cases important for Alzheimer’s research?
Researchers studying simpler genetic forms of dementia, such as FTD driven by tau protein malfunctions, gain insights into how tau impacts behavior and cognitive function, which helps inform treatments for broader age-related brain impairments like Alzheimer’s.
Are there treatments available for genetic frontotemporal dementia?
There is currently no cure, but tau-targeting drugs are in testing phases, and scientists are exploring gene therapy and gene editing to address specific mutations.
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