When a snowball rolls down a mountain, it grows bigger and gains momentum, making it progressively harder to stop. Treating Alzheimer’s disease may be challenging because of a similar “snowball effect” in the brain. Alzheimer’s proteins start to build up in the brain as many as two decades before symptoms start, causing damage to the brain long before it becomes visible.

Could stopping the pre-symptomatic build-up of these proteins in the brain be the key to stopping the disease process and curing Alzheimer’s? Some researchers think that, indeed, the reason new disease-modifying Alzheimer’s drugs don’t have a larger impact is that they intervene too late. 

Now, researchers are running trials, observing the effects of these types of drugs on healthy people to see if administering treatments earlier could prevent or slow the progression of Alzheimer’s disease.  

AHEAD 3-45: Leqembi for Alzheimer’s prevention

In the Phase 3 trial of Biogen and Eisai’s anti-amyloid drug Leqembi, the participants who had less severe symptoms at the start of the study appeared to benefit more from the treatment. 

The two ongoing trials tested whether four years of Leqembi treatment could prevent cognitively healthy people with beta-amyloid plaques in their brains from developing Alzheimer’s symptoms. 

The Phase 2 trial within AHEAD 3 trial examines the effects of Leqembi on beta-amyloid in people with intermediate levels of plaque in the brain. The Phase 3 AHEAD 45 trial tests whether the drug could halt the disease in people with high levels of beta-amyloid plaques.

The study includes 1,400 participants. It is expected to conclude in late 2028.  

DIAN-TU-002: Remternetug for Alzheimer’s prevention

Eli Lilly is developing a new anti-amyloid drug called remternetug. While the company is testing the drug in people with early Alzheimer’s disease, researchers at the Washington University School of Medicine are also looking at whether it can prevent the disease altogether in a trial called DIAN-TU-002. 

This long-term Phase 2/3 clinical study is enrolling 240 participants as young as 18 who have Alzheimer’s in their families and may be a decade out from developing symptoms. This trial will test remternetug against a placebo for 3.5 years, giving all participants the option to take the drug after the study ends. Results from this study are expected in 2034.

Trials for Alzheimer’s vaccines

AC Immune SA is testing two different Alzheimer’s vaccines. In partnership with Takeda, AC Immune is testing whether an amyloid-targeting vaccine called ACI-24.060 could prevent Alzheimer’s disease in people with Down syndrome. As many as 90 percent of people with Down syndrome develop an early-onset form of the disease. The trial will test the vaccine in 140 people over 1.5 years to confirm its safety and its ability to clear amyloid plaques. The results are expected in 2026. If successful, a Phase 3 trial would follow.

In partnership with Jannsen, AC Immune is also planning a Phase 2 study to test whether its experimental tau vaccine JNJ-2056 could prevent Alzheimer’s. The four-year trial will involve 498 cognitively healthy participants. It has yet to commence. Whether or not these trials ultimately succeed, they will provide important data about the role of plaques in disease progression, possibly opening the door to new strategies for treating Alzheimer’s.