Characterization and super-resolution imaging of small tau aggregates in human samples

The hyperphosphorylation and aggregation of the microtubule binding protein tau plays a key role in the development of Alzheimer’s disease and other tauopathies, ultimately resulting in the formation of intracellular tau filaments. While the structure of the filaments formed in humans has recently been determined to atomic resolution, there is far less information available about the smaller aggregates formed in earlier stages of the aggregation process, thought to be the toxic species. To address this problem, we have adapted single molecule pull-down experiments to detect tau aggregates in human brain homogenate and serum. We report the number of aggregates as well as their size and shape measured via super-resolution imaging. Using antibodies to particular phosphorylation sites (pT181, AT8), we can also measure the extent of post-translational modification of individual aggregates. This methodology will enable detailed studies of tau aggregates that formed during disease and has the potential for early diagnosis of disease. ### Competing Interest Statement The authors have declared no competing interest.