A Subset of Alzheimer’s Cases May Be Caused by Two Copies of a Single Gene, New Research Shows

A section of a human brain with Alzheimer's disease is displayed at the Museum of Neuroanatomy at the University at Buffalo, in Buffalo, N.Y., Oct. 7, 2003. (AP)
A section of a human brain with Alzheimer's disease is displayed at the Museum of Neuroanatomy at the University at Buffalo, in Buffalo, N.Y., Oct. 7, 2003. (AP)
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A Subset of Alzheimer’s Cases May Be Caused by Two Copies of a Single Gene, New Research Shows

A section of a human brain with Alzheimer's disease is displayed at the Museum of Neuroanatomy at the University at Buffalo, in Buffalo, N.Y., Oct. 7, 2003. (AP)
A section of a human brain with Alzheimer's disease is displayed at the Museum of Neuroanatomy at the University at Buffalo, in Buffalo, N.Y., Oct. 7, 2003. (AP)

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.

Among them: Symptoms can begin seven to 10 years sooner than in other older adults who develop Alzheimer’s.

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.

RESEARCH POINTS TO A CAUSE FOR A SUBSET OF ALZHEIMER'S 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 US 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.



Puppies Rescued from Flood-Stricken Texas Arrive at Chicago Shelter

 A couple watches a storm passes in the distance, Tuesday, July 15, 2025, in San Antonio. (AP)
A couple watches a storm passes in the distance, Tuesday, July 15, 2025, in San Antonio. (AP)
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Puppies Rescued from Flood-Stricken Texas Arrive at Chicago Shelter

 A couple watches a storm passes in the distance, Tuesday, July 15, 2025, in San Antonio. (AP)
A couple watches a storm passes in the distance, Tuesday, July 15, 2025, in San Antonio. (AP)

Nine puppies from parts of Texas submerged by catastrophic flooding that killed at least 132 people arrived Wednesday at the no-kill shelter PAWS Chicago, joining dozens of puppies that had already arrived.

The critters landed by plane at Waukesha Airport in Wisconsin then made a three-hour journey by van to Chicago.

This is the second batch of pets to arrive in Chicago from Texas. The group Austin Pets Alive!, which has been on the ground in the flood-stricken region since the flooding began, has coordinated the effort with PAWS Chicago.

The animals were in shelters in Texas before the floods began. Organizers say the transfers help those shelters focus on rescuing and reunifying animals separated from their humans by the disaster.

"We’re really happy to be able to support the area by freeing up really needed space in their shelters so they are able to open their shelters to displaced pets," said Celene Mielcarek, PAWS Chicago head of program operations.

PAWS Chicago’s disaster relief program began in 2005 when the organization took in more than 200 pets in the wake of Hurricane Katrina, according to the shelter. Since then, PAWS has rescued pets from areas impacted by Hurricane Helene last year and rescued 33 dogs from Houston shelters after storms in 2023.

Peter Brown, a PAWS volunteer who drove to collect the dogs in Waukesha, said they were anxious on the trip but settled in quickly. He is hopeful the dogs will be quickly adopted.

"They’ll find good homes here," he said. "And then some family who lost their dog in the floods will get it back."

On Monday night, 22 dogs arrived in Chicago from Concho Valley PAWS, a rescue organization in San Angelo, Texas. A total of 31 dogs, ranging from six weeks old to adult dogs, have been relocated to Chicago.

The dogs began receiving medical attention immediately after arriving at PAWS, including being vaccinated, microchipped, and spayed or neutered. They may be ready for adoption and fostering within a few days, according to PAWS.

But for now, they'll get some well-deserved rest, Mielcarek said.

"They’re all pretty tired," she said. "They’re all ready for their dinner."