Study: Gene May Cause Alzheimer’s in Some Cases

20 May 2024

For the first time, researchers have identified a genetic form of late-in-life Alzheimer's disease.

Alzheimer's is a disease of the brain that causes people to lose their memory and mental abilities as they grow old.

Scientists have long known a gene called APOE4 is one of the many things that can increase a person's risk for Alzheimer's.

FILE - 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 Photo/David Duprey, File)
FILE - 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 Photo/David Duprey, File)

One risk includes simply getting old; most Alzheimer's cases appear after age 65. But new research suggests that a cause of the disease is carrying two copies of the APOE4 gene. People with two copies of APOE4 inherited the gene from both parents.

Those patients may experience signs of Alzheimer's seven to 10 years sooner than other adults who develop Alzheimer's, the research found.

Dr. Juan Fortea led the study. He is with the Sant Pau Reasearch Institute in Barcelona, Spain. He said the findings mark a difference with "profound implications."

An estimated 15 percent of Alzheimer's patients carry two copies of APOE4. 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 kinds that appear at much younger ages. They were also thought to make up less than one percent of all cases.

Scientists say the new research shows the importance of developing treatments that target the APOE4 genes.

Dr. Reisa Sperling is with Harvard's Brigham and Women's Hospital in Boston. She helped write the study, which appeared recently in the publication Nature Medicine.

She said some doctors will not offer the only drug that has been shown to slow the disease, Leqembi, to people with the gene pair. She said that they are not offered the drug because those patients are at an especially high risk of developing a dangerous side effect.

Sperling studies ways to prevent or at least delay Alzheimer's. She said, "This data for me says wow, what an important group to be able to go after before they become symptomatic."

But the news does not mean people should race for a gene test. She told The Associated Press, "It's important not to scare everyone who has a family history" of Alzheimer's. She said the gene pair is not the cause of most cases of the disease.

How do genetics affect Alzheimer's?

More than 6 million Americans, and millions more worldwide, have Alzheimer's. Some genes are known to cause rare "early-onset forms." This is where changes in the genes are passed through families that can cause symptoms to appear by age 50.

But Alzheimer's most commonly appears after 65. Most cases begin after the age of 70. The APOE gene was known to play some part.

Most people carry the APOE3 gene that appears to neither increase nor decrease Alzheimer's risk. Some carry APOE2, which provides some protection against Alzheimer's.

APOE4 has long been called the biggest genetic risk factor for late-in-life Alzheimer's, with two copies riskier than one. About two percent of the world's population is estimated to have a copy of the gene from both parents.

Research points to a cause for a kind of Alzheimer's

Fortea's team used data from over 3,000 brains donated for research and from more than 10,000 people in U.S. and European Alzheimer's studies. The team's aim was to better understand genes' role in Alzheimer's. They examined symptoms and early signs of Alzheimer's such as sticky amyloid in the brain.

Amyloid is a protein that can exist in different body parts, including the brain, with certain diseases.

The researchers found that people with two APOE4 copies were gaining more amyloid at age 55 than those with just one copy of APOE4. They were also gaining more amyloid than people who had the "neutral" APOE3 gene.

By age 65, brain imaging showed large amounts of harmful amyloid buildup in nearly 75 percent of individuals with two copies of APOE4. Those individuals were also more likely to have beginning Alzheimer's symptoms by that age rather than later in life.

Sperling noted that not everyone with two APOE4 genes develops Alzheimer's symptoms. Researchers hope to learn why.

How the new findings may affect Alzheimer's research and treatment

The drug Leqembi works by clearing away some amyloid in patients' brains. But Sperling said it is not clear if carriers of two APOE4 genes gain from taking the drug. That is because they have such a high risk of brain swelling and bleeding.

One research question is whether patients with two APOE4 genes should start such drugs sooner than other people.

Dr. Eliezer Masliah of the National Institute on Aging said other research aims to develop gene therapy or drugs that target APOE4. He said it is important to understand APOE4's effects in different populations. So far, studies related to APOE4 have mostly involved white people of European ancestry.

I'm Anna Matteo. And I'm Gregory Stachel.

Lauran Neergaard reported this story for The Associated Press. Gregory Stachel adapted it for VOA Learning English.


Words in This Story

profound – adj. very great

implications – n. a possible future effect or result

symptoms – n. a change in the body or mind which indicates that a disease is present

track – v. to follow and find (someone or something) especially by looking at evidence

factor – n. something that helps produce or influence a result

swelling – adj. something that helps produce or influence a result

therapy – n. the treatment of physical or mental illnesses