Tau forms oligomeric complexes on microtubules that are distinct from tau aggregates

Melina Theoni Gyparaki, Arian Arab, Elena M. Sorokina, Adriana N. Santiago-Ruiz, Christopher H. Bohrer, Jie Xiao, Melike Lakadamyali

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1 Scopus citations


Tau is a microtubule-associated protein, which promotes neuronal microtubule assembly and stability. Accumulation of tau into insoluble aggregates known as neurofibrillary tangles (NFTs) is a pathological hallmark of several neurodegenerative diseases. The current hypothesis is that small, soluble oligomeric tau species preceding NFT formation cause toxicity. However, thus far, visualizing the spatial distribution of tau monomers and oligomers inside cells under physiological or pathological conditions has not been possible. Here, using single-molecule localization microscopy, we show that tau forms small oligomers on microtubules ex vivo. These oligomers are distinct from those found in cells exhibiting tau aggregation and could be precursors of aggregated tau in pathology. Furthermore, using an unsupervised shape classification algorithm that we developed, we show that different tau phosphorylation states are associated with distinct tau aggregate species. Our work elucidates tau's nanoscale composition under nonaggregated and aggregated conditions ex vivo.

Original languageEnglish (US)
Article numbere2021461118
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number19
StatePublished - May 11 2021


  • Protein aggregation
  • Super-resolution microscopy
  • Tau

ASJC Scopus subject areas

  • General


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