Can a Drug Prevent Alzheimer’s Disease Decades Before It Happens?

A clinical trial has just begun that might take decades to fully complete but could have life-changing results. Researchers are testing out a plaque-clearing drug for Alzheimer’s disease in young people who are genetically destined to develop the devastating brain disorder.

Researchers at the Washington University School of Medicine are leading the study, which is testing an experimental antibody developed by the pharmaceutical company Eli Lilly. The drug is being given to people as young as 18 who are at high risk for early onset Alzheimer’s. Though it may take up to 25 years to truly know whether these drugs can work as hoped, it will take much less time to gain some valuable insights into the nature of Alzheimer’s, the researchers say.

The drug being used in the trial is called remternetug. It’s intended to be a successor to Eli Lilly’s donanemab (brand name Kisunla), which was approved to treat early Alzheimer’s disease in July 2024. Donanemab, remternetug, and similar drugs try to treat Alzheimer’s by targeting a misfolded version of the protein amyloid beta. In people with Alzheimer’s, this misfolded amyloid beta builds up in the brain, eventually forming into hardy clumps known as plaques (another misfolded protein, tau, also plays a key role in causing Alzheimer’s).

While anti-amyloid drugs are the first approved treatments thought to delay the progression of Alzheimer’s, the current therapies only have a modest effect. It’s known that amyloid plaques can start building up in the brain 20 or more years before someone starts to show signs of Alzheimer’s, however. And that’s led to speculation these drugs might be substantially more effective and could even prevent Alzheimer’s altogether if given to high-risk people during the earlier time frame—a hypothesis that this newest trial aims to test directly.

The study, called the Primary Prevention Trial, will enroll 240 people from families who are known to carry mutations in one of three genes that almost always result in early-onset Alzheimer’s. It will include people who carry these mutations as well as non-carrier relatives who will act as a sort of control group. People are eligible to be in the study if they’re 11 to 25 years younger than the age they would be expected to develop Alzheimer’s based on their family history (typically this happens in people’s 30s, 40s, or 50s).

The main part of the trial will run for two years, with participants randomized to receive the drug or a placebo every three months. Afterward, people will be able to openly take the drug for another four years if they so choose. Because the volunteers are so young, the researchers don’t expect to see any changes in their cognition during the trial. But they will be able to see whether remternetug can noticeably slow down or even stop the build up of amyloid plaque in people’s brains.

“My grandfather passed away from Alzheimer’s, and so did his mother and all but one of his brothers,” said Hannah Richardson, 24, a participant in the Primary Prevention Trial, in a statement provided by the Washington University School of Medicine. “I am happy to be involved in the Primary Prevention Trial and be involved in research because I know how important it is.”

The researchers say it will take roughly four to five years to report findings from the first placebo-controlled stage of the trial, while the entire study is on track to be completed by 2034. But they plan to keep an eye on these patients for many years afterward. And the lessons we learn from this research are likely to help scientists better understand both early-onset and classic Alzheimer’s.

“This innovative study in this special Alzheimer’s patient population has the potential to significantly impact how we prevent Alzheimer’s disease, saving individuals and families from the anguish of this fatal disease,” said Maria C. Carrillo, chief science officer at the Alzheimer’s Association, in a statement.