Fig. 8. Proposed hypothetical model of tau liquid–liquid phase separation in normal and pathological conditions.

a Under normal physiological conditions, phase separation could lead to the formation of tau liquid droplet-like structures that show high dynamics. b Forms of tau associated with disease, such as phosphorylated tau (e.g. at the AT8 site) or mutant tau that causes inherited tauopathies, facilitate liquid droplet formation. c Pathological conditions that facilitate tau phase separation and/or prolong phase separation may lead to the adoption of pathological tau conformations (i.e. PAD exposure and oligomerization) that have been linked to cell toxicity.