Scientists’ discovery could stop Alzheimer’s in its tracks

Scientists have discovered how two types of toxic amyloid-beta particles form as brain plaques develop, which could pave the way for earlier treatment of the devastating disease.

People with Alzheimer’s develop deposits, or plaques, in the brain made largely from a protein called amyloid-beta. 

But plaques are the end point of a long process that can begin decades before Alzheimer’s symptoms appear. For someone diagnosed with Alzheimer’s at around 70 years of age, the amyloid changes may have started in their mid 40s. During this time, smaller particles form that are thought to do much of the damage to brain cells.

Those particles are rare and short-lived, which has made them very difficult to study, and has cast doubt over whether those seen in laboratory experiments are the same as those in the human brain. 

Led by researchers at the University of Sheffield, and published in Nature Communications , scientists developed a method that examines these toxic, short-lived amyloid-beta particles one at a time. 

This allowed them to identify two distinct toxic ‘fingerprints’ in laboratory settings and determine the different routes through which these damaging particles form as amyloid plaques develop. 

Crucially the same toxic fingerprints were observed across studies in the laboratory, in mice and in donated human brain tissue. This supports the evidence that the routes mapped in the laboratory also operate in people with the disease.  

This gives a new hope for treatments that could stop the disease in its tracks before extensive brain damage occurs. While some existing therapies can remove amyloid-beta plaques, the benefits are limited because deposits start forming decades before a person develops symptoms. Intervening at the point where the damaging particles are made, rather than at the deposits they eventually form, offers a way to act much earlier.

Dr Suman De, Senior Research Fellow at the University of Sheffield’s School of Medicine and Population Health, said: “Alzheimer’s disease ruins lives and, sadly, current treatments have only limited efficacy. By the time current treatment begins, a great deal of damage has already been done, and clearing plaques at that stage cannot restore brain cells that have been lost.

“What we've found are targets that exist much earlier - the routes that form the damaging particles in the first place. Understanding those routes gives future researchers something new to aim before extensive deposits and brain cell damage appear.

“If we can interfere with these routes, we may be acting before extensive harm occurs, rather than after it. Although our research is in its infancy, these findings open up promising possibilities of future treatments.”

The team tested whether interfering with these routes would help and used BRICHOS R221E, an engineered version of a naturally occurring protective protein, developed at Karolinska Institutet in Sweden.

In mice, it reduced the levels of both damaging species, along with plaque build-up, brain inflammation and memory problems. 

Rather than clearing deposits that have already formed, it acts on the routes that produce the toxic particles in the first place. 

The approach is not limited to Alzheimer's. The same method could be applied to other conditions in which proteins misfold and clump together.

Researchers at the University of Sheffield worked with colleagues at Karolinska Institutet, Sweden, ETH Zurich and the University of Cambridge.

The research was shaped by individual expertise, while benefiting from collaboration across teams and partners.

To view the full paper, please visit: https://doi.org/10.1038/s41467-026-79028-0