Health
Some Alzheimer's cases may be caused by copies of a single gene, research shows
- Researchers have identified a genetic form of late-in-life Alzheimer’s disease for the first time, which occurs in people inheriting two copies of the APOE4 gene.
- APOE4 is known to increase the risk of Alzheimer’s.
- Symptoms in those with two APOE4 copies can manifest seven to ten years earlier compared to those with other risk factors.
For the first time, researchers have identified a genetic form of late-in-life Alzheimer’s disease — in people who inherit two copies of a worrisome gene.
Scientists have long known a gene called APOE4 is one of many things that can increase people’s risk for Alzheimer’s, including simply getting older. The vast majority of Alzheimer’s cases occur after age 65. But research published Monday suggests that for people who carry not one but two copies of the gene, it’s more than a risk factor, it’s an underlying cause of the mind-robbing disease.
The findings mark a distinction with “profound implications,” said Dr. Juan Fortea, who led the study the Sant Pau Research Institute in Barcelona, Spain.
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Among them: Symptoms can begin seven to 10 years sooner than in other older adults who develop Alzheimer’s.
For the first time, researchers have identified a genetic form of late-in-life Alzheimer’s disease — in people who inherit two copies of a worrisome gene. (AP Photo/David Duprey, File)
An estimated 15% of Alzheimer’s patients carry two copies of APOE4, meaning those cases “can be tracked back to a cause and the cause is in the genes,” Fortea said. Until now, genetic forms of Alzheimer’s were thought to be only types that strike at much younger ages and account for less than 1% of all cases.
Scientists say the research makes it critical to develop treatments that target the APOE4 gene. Some doctors won’t offer the only drug that has been shown to modestly slow the disease, Leqembi, to people with the gene pair because they’re especially prone to a dangerous side effect, said Dr. Reisa Sperling, a study coauthor at Harvard-affiliated Brigham and Women’s Hospital in Boston.
Sperling hunts ways to prevent or at least delay Alzheimer’s and “this data for me says wow, what an important group to be able to go after before they become symptomatic.”
But the news doesn’t mean people should race for a gene test. “It’s important not to scare everyone who has a family history” of Alzheimer’s because this gene duo isn’t behind most cases, she told The Associated Press.
HOW DO GENETICS AFFECT ALZHEIMER’S?
More than 6 million Americans, and millions more worldwide, have Alzheimer’s. A handful of genes are known to cause rare “early-onset” forms, mutations passed through families that trigger symptoms unusually young, by age 50. Some cases also are linked to Down syndrome.
But Alzheimer’s most commonly strikes after 65, especially in the late 70s to 80s, and the APOE gene – which also affects how the body handles fats — was long known to play some role. There are three main varieties. Most people carry the APOE3 variant that appears to neither increase nor decrease Alzheimer’s risk. Some carry APOE2, which provides some protection against Alzheimer’s.
APOE4 has long been labeled the biggest genetic risk factor for late-in-life Alzheimer’s, with two copies risker than one. About 2% of the global population is estimated to have inherited a copy from each parent.
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To better understand the gene’s role, Fortea’s team used data from 3,297 brains donated for research and from over 10,000 people in U.S. and European Alzheimer’s studies. They examined symptoms and early hallmarks of Alzheimer’s such as sticky amyloid in the brain.
People with two APOE4 copies were accumulating more amyloid at age 55 than those with just one copy or the “neutral” APOE3 gene variety, they reported in the journal Nature Medicine. By age 65, brain scans showed significant plaque buildup in nearly three-quarters of those double carriers – who also were more likely to have initial Alzheimer’s symptoms around that age rather than in the 70s or 80s.
Fortea said the disease’s underlying biology was remarkably similar to young inherited types.
It appears more like “a familial form of Alzheimer’s,” said Dr. Eliezer Masliah of the National Institute on Aging. “It is not just a risk factor.”
Importantly, not everyone with two APOE4 genes develops Alzheimer’s symptoms and researchers need to learn why, Sperling cautioned.
“It’s not quite destiny,” she said.
HOW THE NEW FINDINGS MAY AFFECT ALZHEIMER’S RESEARCH AND TREATMENT
The drug Leqembi works by clearing away some sticky amyloid but Sperling said it’s not clear if carriers of two APOE4 genes benefit because they have such a high risk of a side effect from the drug – dangerous brain swelling and bleeding. One research question is whether they’d do better starting such drugs sooner than other people.
Masliah said other research aims to develop gene therapy or drugs to specifically target APOE4. He said it’s also crucial to understand APOE4’s effects in diverse populations since it’s been studied mostly in white people of European ancestry.
As for gene tests, for now they’re typically used only to evaluate if someone’s a candidate for Leqembi or for people enrolling in Alzheimer’s research – especially studies of possible ways to prevent the disease. Sperling said the people most likely to carry two APOE4 genes had parents who both got Alzheimer’s relatively early, in their 60s rather than 80s.
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In a dramatic turn of events that’s captured the attention of animal lovers worldwide, Punch — the young macaque at a zoo in Japan famous for his inseparable bond with a stuffed orangutan toy — has reached a major milestone in his journey toward social integration.
On Thursday, visitors and staff at the Ichikawa Zoological and Botanical Garden witnessed a breakthrough: Punch was seen cuddling with and hitching a ride on the back of a fellow macaque.
Punch’s story began with hardship. He was abandoned by his mother shortly after his birth in July 2025 — and to ensure his survival, zookeepers stepped in to hand-rear the primate.
On Jan. 19, 2026, the zoo officially began the process of reintegrating Punch into the “monkey mountain” enclosure.
The transition was initially fraught with tension.
Punch’s story began with hardship when he was abandoned by his mother shortly after he was born. To help him, zookeepers gave him a stuffed toy that he began dragging around everywhere he went. (David Mareuil/Anadolu via Getty Images)
As a hand-reared infant, Punch was bullied and ignored by the established group of monkeys.
He was often seen huddled alone with his orange plush companion while the rest of the troop interacted.
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In an official statement released Feb. 27, the Ichikawa Zoological and Botanical Garden detailed the meticulous care behind this process.
Previous viral videos showed Punch bullied by the rest of the troop, running to his plushy toy for comfort. (David Mareuil/Anadolu via Getty Images)
“From an animal welfare perspective, our primary goal is to reintegrate Punch with the troop,” the zoo said.
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The strategy involved nursing Punch within the enclosure, so the troop could recognize him as one of their own, and pairing him with a gentle young female macaque prior to his full release to build his confidence.
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The latest footage, captured by X user @tate_gf, suggested the zoo’s patience is paying off.
The video shows Punch seeking physical contact not from his toy, but from another monkey — eventually climbing onto its back for a vital social behavior for young macaques: the “piggyback ride.”
The zoo’s strategy appears to be paying off: Punch, shown at far left, was recently seen riding on the back of a fellow macaque. (David Mareuil/Anadolu via Getty Images)
While Punch still carries his stuffed toy for comfort during moments of perceived danger, the zoo remains optimistic about his progress.
The organization cited the successful 2009 case of Otome, another hand-reared macaque who eventually outgrew her stuffed toy, successfully integrated — and went on to raise four offspring of her own.
The zoo has had crowds coming to see Punch, with hundreds of people lining up to get inside to see the young star, according to reports.
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“I’m hoping Punch has a good life like everybody else does, and think he’s a cute little guy,” one person commented online.
“Such a precious baby,” another person wrote.
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This story discusses suicide. If you or someone you know is having thoughts of suicide, please contact the Suicide & Crisis Lifeline at 988 or 1-800-273-TALK (8255).
Artificial intelligence has been touted as a boon to healthcare, but a new study has revealed its potential shortcomings when it comes to giving medical advice.
In January, OpenAI launched ChatGPT Health, the medical-focused version of the popular chatbot tool.
The company introduced the tool as “a dedicated experience that securely brings your health information and ChatGPT’s intelligence together, to help you feel more informed, prepared and confident navigating your health.”
But researchers at the Icahn School of Medicine at Mount Sinai have found that the tool failed to recommend emergency care for a “significant number” of serious medical cases.
The study, published in the journal Nature Medicine on Feb. 23, aimed to explore how ChatGPT Health — which is reported to have about 40 million users daily — handles situations where people are asking whether to seek emergency care.
Artificial intelligence has been touted as a boon to healthcare, but a new study has revealed its potential shortcomings when it comes to giving medical advice. (iStock)
“Right now, no independent body evaluates these products before they reach the public,” lead author Ashwin Ramaswamy, M.D., instructor of urology at the Icahn School of Medicine at Mount Sinai in New York City, told Fox News Digital.
“We wouldn’t accept that for a medication or a medical device, and we shouldn’t accept it for a product that tens of millions of people are using to make health decisions.”
Emergency scenarios
The team created 60 clinical scenarios across 21 medical specialties, ranging from minor conditions to true medical emergencies.
Three independent physicians then assigned an appropriate level of urgency for each case, based on published clinical practice guidelines in 56 medical societies.
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The researchers conducted 960 interactions with ChatGPT Health to see how the tool responded, taking into account gender, race, barriers to care and “social dynamics.”
While “clear-cut emergencies” — such as stroke or severe allergy — were generally handled well, the researchers found that the tool “under-triaged” many urgent medical issues.
The team created 60 clinical scenarios across 21 medical specialties, ranging from minor conditions to true medical emergencies. (iStock)
For example, in one asthma scenario, the system acknowledged that the patient was showing early signs of respiratory failure — but still recommended waiting instead of seeking emergency care.
“ChatGPT Health performs well in medium-severity cases, but fails at both ends of the spectrum — the cases where getting it right matters most,” Ramaswamy told Fox News Digital. “It under-triaged over half of genuine emergencies and over-triaged roughly two-thirds of mild cases that clinical guidelines say should be managed at home.”
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Under-triage can be life-threatening, the doctor noted, while over-triage can overwhelm emergency departments and delay care for those in real need.
Researchers also identified inconsistencies in suicide risk alerts. In some cases, it directed users to the 988 Suicide and Crisis Lifeline in lower-risk scenarios, and in others, it failed to offer that recommendation even when a person discussed suicidal ideations.
“ChatGPT Health performs well in medium-severity cases, but fails at both ends of the spectrum.”
“The suicide guardrail failure was the most alarming,” study co-author Girish N. Nadkarni, M.D., chief AI officer of the Mount Sinai Health System, told Fox News Digital.
ChatGPT Health is designed to show a crisis intervention banner when someone describes thoughts of self-harm, the researcher noted.
OpenAI launched ChatGPT Health, the medical-focused version of the popular chatbot tool, in January 2026. (Gabby Jones/Bloomberg via Getty Images)
“We tested it with a 27-year-old patient who said he’d been thinking about taking a lot of pills,” Nadkarni said. “When he described his symptoms alone, the banner appeared 100% of the time. Then we added normal lab results — same patient, same words, same severity — and the banner vanished.”
“A safety feature that works perfectly in one context and completely fails in a nearly identical context … is a fundamental safety problem.”
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The researchers were also surprised by the social influence aspect.
“When a family member in the scenario said ‘it’s nothing serious’ — which happens all the time in real life — the system became nearly 12 times more likely to downplay the patient’s symptoms,” Nadkarni said. “Everyone has a spouse or parent who tells them they’re overreacting. The AI shouldn’t be agreeing with them during a potential emergency.”
Fox News Digital reached out to Open AI, creator of ChatGPT, requesting comment.
Physicians react
Dr. Marc Siegel, Fox News senior medical analyst, called the new study “important.”
“It underlines the principle that while large language models can triage clear-cut emergencies, they have much more trouble with nuanced situations,” Siegel, who was not involved in the study, told Fox News Digital.
ChatGPT and other LLMs can be helpful tools, a doctor said, but they “should not be used to give medical direction.” (iStock)
“This is where doctors and clinical judgment come in — knowing the nuances of a patient’s history and how they report symptoms and their approach to health.”
ChatGPT and other LLMs can be helpful tools, Siegel said, but they “should not be used to give medical direction.”
“Machine learning and continued input of data can help, but will never compensate for the essential problem – human judgment is needed to decide whether something is a true emergency or not.”
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Dr. Harvey Castro, an emergency physician and AI expert in Texas, echoed the importance of the study, calling it “exactly the kind of independent safety evaluation we need.”
“Innovation moves fast. Oversight has to move just as fast,” Castro, who also did not work on the study, told Fox News Digital. “In healthcare, the most dangerous mistakes happen at the extremes, when something looks mild but is actually catastrophic. That’s where clinical judgment matters most, and where AI must be stress-tested.”
Study limitations
The researchers acknowledged some potential limitations in the study design.
“We used physician-written clinical scenarios rather than real patient conversations, and we tested at a single point in time — these systems update frequently, so performance may change,” Ramaswamy told Fox News Digital.
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Additionally, most of the missed emergencies happened in situations where the danger depended on how the condition was changing over time. It’s not clear whether the same problem would happen with acute medical emergencies.
Because the system had to choose just one fixed urgency category, the test may not reflect the more nuanced advice it might give in a back-and-forth conversation, the researchers noted.
ChatGPT Health is designed to show a crisis intervention banner when someone describes thoughts of self-harm. (iStock)
Also, the study wasn’t large enough to confidently detect small differences in how recommendations might vary by race or gender.
“We need continuous auditing, not one-time studies,” Castro noted. “These systems update frequently, so evaluation must be ongoing.”
‘Don’t wait’
The researchers emphasized the importance of seeking immediate care for serious issues.
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“If something feels seriously wrong — chest pain, difficulty breathing, a severe allergic reaction, thoughts of self-harm — go to the emergency department or call 988,” Ramaswamy advised. “Don’t wait for an AI to tell you it’s OK.”
The researchers noted that they support the use of AI to improve healthcare access, and that they didn’t conduct the study to “tear down the technology.”
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“These tools can be genuinely useful for the right things — understanding a diagnosis you’ve already received, looking up what your medications do and their side effects, or getting answers to questions that didn’t get fully addressed in a short doctor’s visit,” Ramaswamy said.
“That’s a very different use case from deciding whether you need emergency care. Treat them as a complement to your doctor, not a replacement.”
“This study doesn’t mean we abandon AI in healthcare.”
Castro agreed that the benefits of AI health tools should be weighed against the risks.
“AI health tools can increase access, reduce unnecessary visits and empower patients with information,” he said. “They are not inherently unsafe, but they are not yet substitutes for clinical judgment.”
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“This study doesn’t mean we abandon AI in healthcare,” he went on. “It means we mature it. Independent testing and stronger guardrails will determine whether AI becomes a safety net or a liability.”
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