Detection of Small-Molecule Interactions with Fibrillar Tau Protein Aggregates Using Microscale Thermophoresis

Aggregated fibrillar tau protein is a pathological hallmark of several neurodegenerative diseases. Small molecules that bind to tau fibrils may be applied for their detection and quantification. This is of great importance as they can potentially be used for earlier diagnosis of disease and disease progression. Microscale thermophoresis (MST) enables the detection of biomolecular interactions in an aqueous environment in which no immobilization of either reaction partner is required. Here, an MST assay methodology is described for the detection of the interaction between a variety of small molecules and tau fibrils. The results of this study demonstrate that MST is a practical methodology to quantify interactions between small molecules and tau fibrillar aggregates.