The term synucleinopathies covers a group of neurodegenerative diseases (including Parkinson's disease, Lewy body dementia and multiple system atrophy) characterized by the accumulation of abnormal aggregates of the protein alpha-synuclein in the brain.  

In its normal, soluble and monomeric form, alpha-synuclein plays an important role in the normal development of cognitive functions. In synucleinopathies however, it forms toxic, insoluble, fibrillar aggregates that comprise the primary structural component of "Lewy bodies", a characteristic feature of these diseases. These aggregates propagate from one neuron to another, leaving in their wake progressive and irreversible neural degeneration, the manifestations of which vary according to the synucleinopathy in question.

These fibrillar agglomerations are polymorphic, that is, they take on different forms, called conformational strains, each presenting its own biochemical, structural and physical characteristics. The clinical heterogeneity observed in synucleinopathies suggests that there may be a link between the strains and the different pathological manifestations of the diseases.

To explore that possibility, researchers from the Neurodegenerative Diseases Laboratory (MIRCen) partnered with a team from the American Van Andel Institute to characterize the propagation profiles of five distinct alpha-synuclein conformational strains from the olfactory bulb, a brain region affected early in both Parkinson's disease and Lewy body dementia.

They showed that the five strains propagated from the bulb to distinct regions of the brain known to be affected later in the course of disease. Their analysis of the affected cerebral regions, the speed of propagation to them and the resulting diseases indicated specific pathological processes for each of the five strains. 

The specific conformations of the alpha-synuclein assemblies were also shown to be determinant for the speed of aggregate amplification and propagation within the brain.

This international study opens new doors toward the development of specific therapeutic strategies for the range of synucleinopathies via a more precise characterization of alpha-synuclein aggregates in patients.