Brain Derived Biologically Relevant Tau Oligomers

Neurodegenerative Tauopathies, including Alzheimer’s disease (AD), are characterized by the appearance of extracellular lesions composed of aggregated and post‐translationally modified tau proteins. The resulting tau pathology is an established marker for differential disease diagnosis and staging, a surrogate marker for neurodegeneration, a potential vector for disease propagation, and a source of toxicity in biological models. In comparison to the well‐established methods for isolation/preparation and biochemical and structural characterization of stable tau filaments from tauopathy brain, the characterization of smaller and much dynamic oligomeric tau aggregates has not been investigated to the same degree. As a result, tau oligomers that may associate most closely with disease propagation and toxicity as suggested by a large body of research, are not fully established.