Healthcare (Commonwealth Union) – A groundbreaking study reveals that an experimental drug may lower the risk of Alzheimer’s-related dementia in individuals genetically predisposed to develop the disease in their 30s, 40s, or 50s. Led by the Knight Family Dominantly Inherited Alzheimer Network-Trials Unit (DIAN-TU) at Washington University School of Medicine in St. Louis, this research shows for the first time that early intervention to remove amyloid plaques from the brain, well before symptoms appear, can delay the onset of Alzheimer’s dementia.
Published in The Lancet Neurology on March 19, the international study included 73 participants with rare genetic mutations that lead to the overproduction of amyloid, virtually guaranteeing the development of Alzheimer’s in middle age. Among a subgroup of 22 participants who had no cognitive impairments at the start and received the drug for an average of eight years, the treatment reduced the risk of developing symptoms from nearly 100% to about 50%, according to primary data analysis, with multiple supporting sensitivity analyses confirming the trend.
Amyloid has been a key focus for Alzheimer’s disease as many prior studies have focused on various factors effecting amyloid from genetics to exercise.
“Everyone in this study was destined to develop Alzheimer’s disease and some of them haven’t yet,” explained the senior author Randall J. Bateman, MD, the Charles F. and Joanne Knight Distinguished Professor of Neurology at WashU Medicine. “We don’t yet know how long they will remain symptom-free – maybe a few years or maybe decades. In order to give them the best opportunity to stay cognitively normal, we have continued treatment with another anti-amyloid antibody in hopes they will never develop symptoms at all. What we do know is that it’s possible at least to delay the onset of the symptoms of Alzheimer’s disease and give people more years of healthy life.”
The results offer fresh support for the amyloid hypothesis of Alzheimer’s disease, which suggests that the accumulation of amyloid plaques in the brain is the initial trigger for dementia. According to this theory, removing or preventing the formation of these plaques could halt the onset of symptoms. In this research, Bateman and his team tested the impact of an experimental anti-amyloid drug to determine whether it could prevent dementia development.
The study involved participants from the Knight Family DIAN-TU-001 trial, the world’s first Alzheimer’s prevention study, who then transitioned into an extended phase of the trial where they received an anti-amyloid medication. The ongoing study, headed by Bateman and funded by organizations such as the Alzheimer’s Association, GHR Foundation, and the National Institutes of Health (NIH), began in 2012 with the goal of assessing anti-amyloid drugs as potential preventive treatments for Alzheimer’s. All participants were in the early stages of cognitive decline or showed no symptoms, with ages ranging from 15 years before to 10 years after the typical onset of Alzheimer’s, as determined by their family history.
In 2020, the trial concluded with Bateman and colleagues reporting that gantenerumab, a drug developed by Roche and Genentech, reduced amyloid levels in the brain and showed improvements in certain Alzheimer’s protein markers. However, no cognitive benefits were observed, as the group without symptoms – whether on the drug or a placebo – showed no decline. These mixed results led the team to initiate an open-label extension of the trial to further investigate whether higher doses or prolonged treatment could help prevent or delay cognitive decline.
Bateman expressed his optimism regarding the future of Alzheimer’s prevention, indicating that if late-onset Alzheimer’s prevention trials yield results akin to the DIAN-TU trials, it may be possible to soon see Alzheimer’s preventions accessible to the general public. This could mark the first clinical evidence of potential preventions for those at risk of Alzheimer’s disease. He further indicated that we may be on the cusp of delaying the onset of Alzheimer’s for millions of people.
