Tau aggregation is one of the main hallmarks of Alzheimer’s disease, and can lead to neuronal death. Finding tau aggregation inhibitors are vital for therapeutic treatments but have so far been unsuccessful. An important aspect of in vitro studies of tau is generating structures of filaments that replicate what is found in AD. Tau does not spontaneously aggregate and in vitro needs the presence of a cofactor to polymerize. One potential way to induce tau aggregation is with the use of polyunsaturated fatty acids (PUFAs) such as arachidonic acid. Thirteen different PUFAs will be used to determine if the carbon chain length or number of double bonds can be used to identify patterns of how the PUFA will impact tau aggregation. This can give insight into which PUFAs are potentially making similar or different tau fibril structures. Filaments induced by PUFAs that produce different aggregation patterns will be analyzed through cryo-electron microscopy (Cryo-EM) to determine if AD relevant structures are being produced.
Results showed that the structure of the PUFA does not seem to impact the aggregation patterns. Instead two patterns arose, in which one aggregation continues to increase as concentration of the PUFA increases. The other aggregation increases up to a certain concentration before declining. Utilizing Cryo-EM on filaments induced by PUFAs belonging to different patterns was unsuccessful as the resulting aggregates lacked a twist making it difficult to solve for the molecular structure and unable to determine if disease relevant structures are made by PUFAs.Neuroscience, Developmental and Regenerative Biolog
