Neurodegenerative diseases are characterized by the accumulation of normally soluble proteins into insoluble misfolded aggregates. Although individual proteins are associated with certain disorders, several disease-related proteins are found postmortem in the same patient. A recent study suggests that α-synuclein (α-syn) can promote aggregation of tau, an effect that depends on different strains of α-syn.

Credit: David Mack / Science Source

Virginia M.Y. Lee and her colleagues (Cell 154, 103–117) found that synthetic preformed fibrils of α-syn could seed tau aggregation in vitro and also when injected into the brains of mice overexpressing a mutant form of human tau. This effect was dependent on the sequence of α-syn and the method of fibrillization, suggesting that distinct strains of α-syn can promote tau aggregation. These strains seem to be conformationally distinct, as they show different cleavage patterns when digested with proteinase K. Moreover, in a small subset of patients with Parkinson's disease with dementia, distinct α-syn proteinase K cleavage patterns were found. Taken together, these results suggest that different strains of α-syn may promote distinct pathology in neurodegenerative diseases.