Three siblings, a fatal gene: a family's fight against the early onset of Alzheimers

Copyright © HT Digital Streams Limit all rights reserved. Dominique Mosbergen, The Wall Street Journal 6 min Read June 29, 2025, 04:00 IST brothers and from left) Jacob, Rylee and Hannah Richardson at their grandmother’s home in Montgomery, Ala. Summary among members of the Richardson family who has a mutation in the PSEN1 genus, the average age and its end is 39 possibilities. But the 24-year-old’s plans are clouded by an unthinkable reality-there is a 50% chance of his Alzheimer’s disease develop in her thirties. Hannah’s family has a history of a rare genetic mutation that, when inherited, virtually guarantees that the carrier will die from an aggressive form of Alzheimer’s early in life. It has been found that no drug stops it. But now researchers are investigating a new avenue: Can the treatment delay the memory-robbery memory or even stop by people who are a great risk of developing it? Hannah and her two siblings will help researchers to test the theory. They enter for a new clinical trial led by doctors at Washington University School of Medicine. As part of the hearing, the siblings will eventually find out if they are wearing the deadly gene. “I don’t know if I’m going to save me or my siblings in the trial. But in my head, that’s the least I can do. Research is how healing is found,” says Hannah, who dreams of becoming a doctor assistant and applying for graduate programs. Her brother Jacob, 22, and sister Rylee, 19, are both at university. Unlike most cases of Alzheimer’s, who are unpredictable, “in this population we know who will develop the disease and when they will develop it,” said Heather Snyder, senior vice president of medical and scientific operations at the Alzheimer’s Association, a major financier of the trial. Doctors have identified more than 300 inherited genetic mutations that cause Alzheimer’s early on. These rare genes account for less than 1% of people with the condition, but researchers say that studying families such as the Richardsons can provide insights on how to prevent and treat Alzheimer’s in everyone. Among the people in the Hannah family who wear a mutation in the so-called presenilin-1, or PSEN1, genes, is the average age when the symptoms of Alzheimer’s start 39, according to the family. The disease is aggressive once symptoms occur and the decline is fast, the family said. “I call it the monster,” said Mary Salter, Hannah’s grandmother. Hannah’s grandfather and three of his four brothers died of Alzheimer’s in the early 1940s, shortly after developing symptoms. Hannah’s uncle died last year of the disease at the age of 44. Hannah’s mother, Carrie Richardson, began to show subtle signs of the disease in her early forties. Now at the age of 44, Carrie began to fall spiritually. Carrie’s children remembers the day in 2012 when she learned that she was a carrier of the PSEN1 mutation. Her eyes were red and puffy when she went to fetch the children from school. Printed by Hannah to tell them why, a sob Carrie told them the news in the car. The brothers and sisters, who were all under 12, also remember that he was crying, although he did not fully understand why. Carrie today has expired memory and sometimes struggles to communicate, her children say. Her worsening symptoms forced her to end her work as a preschooler teacher, and this month she began the process of leaving her own home to move into Mary. Carrie and her brother entered a clinical trial that started at Washu Medicine in 2012. The trial has tested whether the early use of experimental medicines that targets a sticky protein in the brain, amyloid, can slow down the progression of Alzheimer’s in people who carried PSEN1 mutations and other rare genes. Hannah’s uncle could not tackle an extension of the hearing because his symptoms became too outspoken, but her mother is still a participant and gets a bi -monthly infusion of an antiamyloid remedy. In a paper published in Lancet Neurology in March, which has the interim results of the extensive trial, Washu Medicine researchers said that the treatment of people like Hannah’s mother with antiamyloid medicine before Alzheimer’s symptoms began, in some cases the risk of developing symptoms. The first antiamyloid medicine was approved by the food and medicine application in 2021. This medicine is clear congestion, or plaques, of amyloid in the brain, which researchers once thought could be the cause of Alzheimer’s. But some doctors have since questioned this hypothesis, as well as whether the benefits of these treatments exceed their risks. The medicine does not stop Alzheimer’s in its tracks, and although it has proven to reduce cognitive decline in some major clinical trials, the slowdown was at best, says Dr. Scott Small, a neurologist at the University of Columbia. Carrie Richardson prepares him to blow candles on her birthday cake, surrounded by her children and mother. “Science now predicts that amyloid plaques are not the root source of Alzheimer’s,” Small said. Swelling and bleeding in the brain is a possible side effect of antiamyloid medicine. Rarely are people dead to this complication. In about half of all patients in the Washu medicine study, some brain wealth and microblades were observable in MRI scans, although researchers said about 95% of participants had no symptoms of the medication. Antiamyloid medicine remains the only FDA-approved treatment available that can change the course of Alzheimer’s. Dr Randall Bateman, a neurologist who led the Washu medicine study, said the early use of the treatments could improve their effectiveness and safety. He said he was optimistic that the build -up of amyloid buildup of amyloid could slow down or even prevent the progress of the disease. Hannah and her siblings believe that antiamyloid medicines helped stop their mother’s Alzheimer’s. The belief urged them to enroll for a similar Washu medicine -clinical trial -one that attempts to treat carriers of rare genes with another experimental antiamyloid medicine, called reminders, many years before they develop symptoms, and in some cases even before amyloid in their brain. Drugmaker Eli Lilly, who makes the drug, said it works similarly to earlier antiamyloid treatments, but has the advantage of being applied as an injection rather than an intravenous infusion. Rylee Richardson, a cheerleader and emerging second at Tulane University, said she and her siblings long and loudly thought to take part in the hearing. They finally decided that this is worth the potential risks. “I will do everything that gives me and my siblings a better chance,” she said. Until now, Rylee and her siblings have decided not to find out if they are wearing the PSEN1 mutation for fear that it could raise their lives. But if they want to participate in the extensive phase of the hearing, they will have to learn the truth. Dr Eric McDade, a colleague of Bateman’s who leads the trial, will last two years and focus on basic efficiency and safety questions. Only people who test positive for high-risk genetic mutation will be randomized to receive either a low dose of the active agent or placebo. For those who test negatively, they can stay in the trial if they choose not to find out their genetic status and get a placebo. Dr. Richard Isaacson, a neurologist at the Institute of Neurodegenerative Diseases that is not involved in the hearing, said he believes that antiamyloid medicine can be useful to delay cognitive decline if it is preventively used in patients who have the risk of Alzheimer’s. He himself prescribes themselves to patients in his clinics in New York and Florida, but only in people who have already built up a little amyloid. He questions whether it makes sense to use these drugs in people who do not have amyloid at all. “It’s not something that sits well with me,” Isaacson said. Washu medicine researchers said that antiamyloid treatments in animal experiments were most effective when used before evidence of amyloid builds. But such an experiment still needs to be carried out in people. Alzheimer’s was a ghost that haunted the Richardson brothers and sisters since they were children. The three of them made an agreement years ago not to have children if they learned that they had carried the Alzheimer’s no. “We decided that we would be the last three. No one needs to suffer from our family anymore,” Hannah said. “We want to do everything in our power to stop it for us and everyone else.” Catch all the business news, market news, news reports and latest news updates on Live Mint. Download the Mint News app to get daily market updates. More Topics #Healthcare Read Next Story