WASHINGTON (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.
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.
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.
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.
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Educational Media Group. The AP is solely responsible for all content.
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. A long-feared gene appears to do more than raise people’s risk of Alzheimer’s: Inheriting two copies can cause the mind-robbing disease, according to research published in the journal Nature Medicine on Monday, May 6, 2024. (AP Photo/David Duprey, File)
COLUMBIA, S.C. (AP) — South Carolina is set to execute its first inmate in 13 years after an unintended pause because the state could not obtain the drugs needed for lethal injections.
Freddie Eugene Owens, 46, is scheduled to die just after 6 p.m. Friday at a Columbia prison. He was convicted of the 1997 killing of a clerk who could not get the safe open at a convenience store in Greenville.
Owens’ last-ditch appeals have been repeatedly denied, including by a federal court Friday morning. Owens has also petitioned for a stay of execution from the U.S. Supreme Court. South Carolina's governor and corrections director swiftly filed a reply, stating the high court should reject Owens' petition. The filing said nothing is exceptional about his case.
The scheduled 6 p.m. time of the execution passed as state officials awaited a decision from the high court.
His last chance to avoid death is for Republican South Carolina Gov. Henry McMaster to commute his sentence to life in prison.
McMaster said he will follow historical tradition and announce his decision minutes before the lethal injection begins when prison officials call him and the state attorney general to make sure there is no reason to delay the execution. The former prosecutor promised to review Owens’ clemency petition but has said he tends to trust prosecutors and juries.
Owens may be the first of several inmates to die in the state's death chamber at Broad River Correctional Institution. Five other inmates are out of appeals and the South Carolina Supreme Court has cleared the way to hold an execution every five weeks.
South Carolina first tried to add the firing squad to restart executions after its supply of lethal injection drugs expired and no company was willing to publicly sell them more. But the state had to pass a shield law keeping the drug supplier and much of the protocol for executions secret to be able to reopen the death chamber.
To carry out executions, the state switched from a three-drug method to a new protocol of using just the sedative pentobarbital. The new process is similar to how the federal government kills inmates, according to state prison officials.
South Carolina law allows condemned inmates to choose lethal injection, the new firing squad or the electric chair built in 1912. Owens allowed his lawyer to choose how he died, saying he felt if he made the choice he would be a party to his own death and his religious beliefs denounce suicide.
Owens changed his name to Khalil Divine Black Sun Allah while in prison but court and prison records continue to refer to him as Owens.
Owens was convicted of killing Irene Graves in 1999. Prosecutors said he fired a shot into the head of the single mother of three who worked three jobs when she said she couldn't open the store's safe.
But hanging over his case is another killing: After his conviction, but before he was sentenced in Graves’ killing, Owens fatally attacked a fellow jail inmate, Christopher Lee.
Owens gave a detailed confession about how he stabbed Lee, burned his eyes, choked and stomped him, ending by saying he did it “because I was wrongly convicted of murder,” according to the written account of an investigator.
That confession was read to each jury and judge who went on to sentence Owens to death. Owens had two different death sentences overturned on appeal only to end up back on death row.
Owens was charged with murder in Lee's death but was never tried. Prosecutors dropped the charges with the right to restore them in 2019 around the time Owens ran out of regular appeals.
In his final appeal, Owens' lawyers said prosecutors never presented scientific evidence that Owens pulled the trigger when Graves was killed and the chief evidence against him was a co-defendant who pleaded guilty and testified that Owens was the killer.
Owens’ attorneys provided a sworn statement two days before the execution from Steven Golden saying Owens was not in the store, contradicting his trial testimony. Prosecutors said other friends of Owens and his former girlfriend testified that he bragged about killing the clerk.
“South Carolina is on the verge of executing a man for a crime he did not commit. We will continue to advocate for Mr. Owens,” attorney Gerald “Bo” King said in a statement.
Owens' lawyers also said he was just 19 when the killing happened and that he had suffered brain damage from physical and sexual violence while in a juvenile prison.
South Carolinians for Alternatives to the Death Penalty plans a vigil outside the prison about 90 minutes before Owens is scheduled to die.
South Carolina’s last execution was in May 2011. It took a decade of wrangling in the Legislature — first adding the firing squad as a method and later passing a shield law — to get capital punishment restarted.
South Carolina has put 43 inmates to death since the death penalty was restarted in the U.S. in 1976. In the early 2000s, it was carrying out an average of three executions a year. Only nine states have put more inmates to death.
But since the unintentional execution pause, South Carolina’s death row population has dwindled. The state had 63 condemned inmates in early 2011. It had 32 when Friday started. About 20 inmates have been taken off death row and received different prison sentences after successful appeals. Others have died of natural causes.
Rev. Hillary Taylor protests the planned execution of Freddie Eugene Owens, 46, on Friday, Sept. 20, 2024, in Columbia, S.C. Owens is set to be the first person to be executed in South Carolina in 13 years. (AP Photo/Chris Carlson)
A demonstrators protests the planned execution of Freddie Eugene Owens, 46, on Friday, Sept. 20, 2024, in Columbia, S.C. Owens is set to be the first person to be executed in South Carolina in 13 years. (AP Photo/Chris Carlson)
Jesse Motte, right, protests the planned execution of Freddie Eugene Owens, 46, on Friday, Sept. 20, 2024, in Columbia, S.C. Owens is set to be the first person to be executed in South Carolina in 13 years. (AP Photo/Chris Carlson)
Rev. Hillary Taylor protests the planned execution of Freddie Eugene Owens, 46, on Friday, Sept. 20, 2024, in Columbia, S.C. Owens is set to be the first person to be executed in South Carolina in 13 years. (AP Photo/Chris Carlson)
South Carolinians for Alternatives to the Death Penalty Executive Director Rev. Hillary Taylor speaks at a news conference before delivering petitions to stop the execution of Freddie Owens at the South Carolina Statehouse in Columbia, S.C., Thursday, Sept. 19, 2024. (AP Photo/Jeffrey Collins)
South Carolina prepares for first execution in 13 years
South Carolinians for Alternatives to the Death Penalty Executive Director Rev. Hillary Taylor speaks at a news conference before delivering petitions to stop the execution of Freddie Owens at the South Carolina Statehouse in Columbia, S.C., Thursday, Sept. 19, 2024. (AP Photo/Jeffrey Collins)
South Carolina prepares for first execution in 13 years
