Researchers have observed accelerated formation of amyloid proteins linked to Alzheimer’s disease for the first time.

According to projections by the World Health Organization, the number of Alzheimer's disease cases worldwide is expected to rise to 78 million by 2030 and reach 139 million by 2050. These alarming statistics underscore the urgent need for new diagnostic and therapeutic approaches for this neurodegenerative condition.  

In this endeavor, a significant breakthrough has been achieved by an international research team from the University of Limerick (Ireland) and the EMPA laboratory (Switzerland), which successfully visualized the processes occurring on the surface of amyloid fibrils (structures in the brain formed by oligomers—soluble, highly toxic proteins for neurons that aggregate into dense, degradation-resistant fibers) and identified a specific subtype of super-spreader proteins among them. The results have been published in the journal Science Advances.  

As a reminder, Alzheimer's disease is characterized by the gradual deterioration of the brain, leading to memory impairment, cognitive dysfunction, and motor function issues due to inflammation, tissue death, and the accumulation of amyloid plaques. While the precise causes of this neurodegenerative disease remain unknown, previous studies have found that individuals vaccinated against influenza, tetanus, polio, and rabies have a significantly lower incidence of developing the corresponding disease.

Beta-amyloids (Aβ-42) are misfolded proteins that contribute to the formation of new oligomers on the surface of existing fibrils through a process known as secondary nucleation (where mature fibrils catalyze the emergence of new oligomers). The team observed the entire process—from initiation to completion—in real time using atomic force microscopy (AFM) over a span of 250 hours. 

The proteins remained in their native form in a saline solution (which closely resembles their natural habitat in the human body). This approach eliminated the risk of structural and behavioral distortions of the proteins due to external interference, and the new visualization method enabled the capture of images of fibrils with a resolution of less than 10 nanometers at room temperature. Previously, traditional analysis methods could alter the morphology and adsorption sites of the proteins. 

To gain a deeper understanding of the interactions between oligomers and fibrils, the experimental observation data were supplemented by molecular modeling techniques. The results identified super-spreader proteins, whose exceptionally high catalytic activity served as a magnet for new oligomers, facilitating the formation of secondary fibrils. This indicates that the accelerated spread of toxic soluble proteins in brain tissues is driven specifically by these super-spreaders.  

“We have made strides in understanding how these proteins propagate in the brain during Alzheimer's disease. The findings could lead to the development of new diagnostic methods for the disease, and understanding the precise mechanisms of toxic oligomer formation will enable the creation of effective therapeutic strategies,” explained one of the authors of the scientific paper, Peter Nirmalraj from the EMPA laboratory. 

Thus, the discovery of super-spreader proteins (and the role they play in the disease's progression) through this innovative visualization technique has far-reaching implications for the diagnosis and therapy of currently incurable neurodegenerative diseases.