Despite the role of amyloid fibrils, and consequently plaques, in Alzheimer’s disease being well-known, the mechanism behind their initial development and then self-replication within the brain has remained unknown. A new study from researchers at the University of Cambridge (UK) has sought to investigate this, highlighting the requirements for protein fibril self-replication, with potential implications for drug development.
The formation of the first amyloid fibrils within the brain occurs spontaneously and slowly, usually taking several decades. However, following the development of these first protein fibrils, replication and spread increases exponentially, resulting in a highly difficult disease to halt the progression of.
Utilizing amyloid-beta, the research team identified a relationship between the quantity of healthy proteins deposited into existing fibrils and the rate of fibril self-replication, indicating a relatively simple mechanism governed by the build-up of healthy proteins on the surface of existing fibrils.
To further test the theory, the team altered the interaction between the healthy proteins and the surface of fibrils, which resulted in an ability to control the rate of self-replication.
First author, Dr Anđela Šarić (University of Cambridge), commented: “this discovery suggests that if we’re able to control the build-up of healthy proteins on the fibrils, we might be able to limit the aggregation and spread of plaques.”