Abstract

Age-related neurodegenerative disorders like Alzheimers disease (AD) and Parkinsons disease (PD) are characterized by deposits of protein aggregates, or amyloid, in various regions of the brain. Traditionally, aggregation of a single protein was observed to be correlated with these different pathologies: tau in AD and -synuclein (S) in PD. However, there is increasing evidence that the pathologies of these two diseases overlap, and the individual proteins may promote each others aggregation. Both tau and S are intrinsically disordered proteins (IDPs), lacking stable secondary and tertiary structure under physiological conditions. In this study we used a combination of biochemical and biophysical techniques to interrogate the interaction of tau with both soluble and fibrillar S. Fluorescence correlation spectroscopy (FCS) was used to assess the interactions of specific domains of fluorescently labeled tau with full length and C-terminally truncated S in both monomeric and fibrillar forms. We found that full-length tau as well as individual tau domains interact with monomer S weakly, but this interaction is much more pronounced with S seeds. This interaction does not impact tau aggregation or fibril formation. These findings provide insight into the nature of interactions between tau and S as well as the domains responsible.