AbstractBackgroundDeposits of hyperphosphorylated Tau Protein is the main feature of Alzheimer disease and these are closely related with cognitive impairment, aggregates can cause neuronal death. Into cells there are mechanisms responsible for maintaining a balance among synthesis and degradation of proteins, named proteostasis mechanisms, one of them is mediated maily by Hsp90. Due to the presence of intracellular protein deposits in Alzheimer disease it is clear that some of the proteostasis fail or is not too efficient.MethodSH‐SY5Y cells were transfected independently with two distinct plasmids containing two different forms of tau protein, one which contains a tau with 14 aminoacid changed for alanine in order to prevent phosphorylation and the other containing the same aminoacid changed for glutamate to mimic phosphorylation, Tau protein expression was analyzed by western blot at different times.The same genes that codified for Tau proteins that were expressed in cell line, were cloned into an expression vector to be expressed in bacteria as recombinant proteins, then protein expression was carried out in E.coli BL21DE3 induced by IPTG, bacterial cells were lysed and recombinant proteins were purified by nickel columns and then quantified. Afterwards overlay assays were developed, various concentrations of the two different types of purified Tau proteins were spotted onto a nitrocellulose membrane. This membrane was incubated with cellular extracts of SHSH‐5Y containing native form of Hsp90. Subsequently, membrane was washed and the protein still bound was detected by inmmunobloting with an antibody recognizing Hsp90. Additionally, Dynamic light scattering light was performed to evaluate if recombinant proteins could produce fibrillation.ResultWe found that diminishing of Tau expression which has glutamates was less than Tau expression containing alanine, at the time of 48h. Overlay assay showed that cellular Hsp90 presented lower binding affinity for recombinant Tau with glutamates. Finally, in Dynamic Light Scattering assay Tau with glutamates presents higher fibrillation than Tau with alanine.ConclusionThese results suggest that binding affinity of Hsp90 for Tau regulates its degradation, this could be the main reason of its accumulation and agreggation into cell. Moreover, phosphorylation in specific sites is closely related with its fibrillation.