It is already known that the misfolded proteins clump together to form fiber-like structures. However, it is not yet fully understood how these fibrils are formed. Now a team led by Empa researcher Peter Nirmalraj from Empa's Transport at Nanoscale Interfaces laboratory and scientists from the Irish University of Limerick have been able to show how the process takes place using a particularly powerful imaging technique.

The special thing about it: Some of the nanometer-thin fibrils apparently ensure the spread of the disease in the brain tissue and are therefore referred to as "superspreaders." The researchers recently published their findings in the journal Science Advances.

Toxic subspecies

This peculiar subspecies of protein fibrils caught the researchers' attention because of its unusual properties: The edges and the surfaces of the so-called superspreader fibrils show a particularly high catalytic activity. New protein building blocks accumulate at these highly active sites. As a result, new, long-chain fibrils form from these nucleation sites. The researchers assume that these second-generation fibrils eventually spread and form new aggregates in the brain.

The chemical composition of the misfolded amyloid β protein is known. The mechanism of how protein building blocks come together to form second-generation fibrils, as well as their shape and structure, was previously unclear. "Conventional methods, such as those based on staining techniques, could alter the morphology and adsorption site of the proteins so that they cannot be analyzed in their natural form," says Nirmalraj.