Tau Aggregation

Crosslinking diagram
Crosslinking studies on inert tau monomer (Mi) and tau seeding monomer (Ms) reveal different crosslink patterns. Ms crosslinks are also more stable when heated.

Tau protein, which normally functions to stabilize the physical framework of cells, sometimes take on a shape that creates tangles in human brains that are linked to neurodegenerative diseases called tauopathies.

We want to understand how the inert form transforms into the pathological shape. A key tool in our research is a technique called cross-linking mass spectrometry (XL-MS), which creates chemical bonds among adjacent portions of the protein to reveal architectural information.

Recently we purified and characterized a conformation of tau monomer that serves as a “seed” that drives aggregation, which we named Ms. Using XL-MS, we found that Ms's shape exposes a portion of the protein that is normally hidden within inert tau monomer (Mi).

We are now studying how different conformations of tau are related to different tauopathies – whether, for instance, tau aggregates in Alzheimer’s disease differ from those in Parkinson’s disease. A clearer understanding of the shapes these conformations adopt will have important implications for development of better diagnostic and therapeutic strategies.


Mirbaha H, et al (2018). Inert and seed-competent tau monomers suggest structural origins of aggregationeLife:e36584.