Researchers at Karolinska Institutet, the University of Sheffield and the University of Cambridge report two distinct forms of small amyloid-beta clusters that appear before plaques develop in Alzheimer's disease and can damage nerve cells. The study was published on 9 November in Nature Communications.
Amyloid-beta is a short peptide that clumps together, and the plaques it forms are a hallmark of the disease. The new work looks earlier, at the small clusters that form before plaques appear.
How the study worked
The team used advanced microscopy and analysed brain tissue from people who had died with Alzheimer's disease, alongside mouse models and cultured nerve cells. The Karolinska press release does not give sample sizes or mouse strains.
What the researchers found
They identified two types of amyloid-beta cluster that can damage nerve cells, present both in human Alzheimer's brain tissue and in the experimental models. The two forms appear to arise in different ways and may play different roles as the disease progresses, and only one of them appears to develop further into plaques.
The group also tested BRICHOS, a protein that Karolinska researchers discovered earlier and that can counteract the formation of the harmful forms. In mouse models, BRICHOS reduced the harmful clusters, plaque formation and brain inflammation, and improved performance in cognitive tests.
Jan Johansson, a professor at Karolinska Institutet and one of the study's lead researchers, says current antibody treatments for Alzheimer's have limited effects, can cause side effects and are costly. He describes preventing the formation of the forms that appear to cause the damage as an alternative approach.
What is still unknown
The release gives no doses, routes, durations or effect sizes for the mouse results, and it reports no human clinical data for BRICHOS. How the two forms damage nerve cells is still to be worked out, and the researchers say more research is needed to understand their roles.
Some Karolinska researchers founded Briccos AB, which KI Innovations co-owns, and the paper discloses potential conflicts of interest. OrientSciences worked from the Karolinska press release and coverage and did not read the paper.