Ur independent samples have been assessed for the 2 fractions. Figure S4. Tau induced hyperphosphorylation doesn’t alter Rac1 levels or activation. (A) Representative confocal photographs of mature cortical neurons treated with 10nM OA for 6h and immunostained against pS262 tau. Scale bar 30 m. (B-C) Tau pS262 phosphorylation was analysed by western blot after three and 6h from OA administration. The data represented are mean with SEM of four or six independent experiments (3h therapy n=6, 6h therapy n=4). (D-E) Rac1-GTP pull done assay was performed following 3 and 6h from OA administration. The information represented are mean with SEM of three independent experiments. ns, not considerable. Asterisks indicate unspecific bands. (DOCX 3215 kb) Acknowledgements We thank prof. C. Laudanna and members of his laboratory for invaluable aid within the preparations of Rac1 mutant peptides. Funding This function was supported by a grant in the Italian Ministry of Well being, Convenzione n.173/GR-2011-02348526 and Ricerca Corrente. SZ is Testican 3 Protein Mouse partially supported by FEDER, project “Digital Analytics Platform”. Availability of information and components The information obtained throughout the existing study is obtainable from the corresponding author on affordable request. Authors’ contributions RG, LB, AP made the experiments on plasma samples. SF and GB recruited and clinically evaluated the individuals. MC and GDF developed the experiments on human brains. CS carried out the human plasma assays and the analyses from the A peptides. VP performed the in vitro experiments using a and OA therapies. MiBo performed the animal analysis along with the in vitro treatments with mutant Rac1 peptides. EL made the Rac1 mutant peptides and performed the internalization experiments with TAT-GFP. MiBo, CS, MC, and PV wrote materials, strategies, and final results of their corresponding element. MaBu, GZ, LB, and RG critically revised the manuscript. SZ performed the bioinformatics analysis. SB conceived the project, coordinated the study, and finalized the manuscript. All authors reviewed and approved the final manuscript. Ethics approval Biological human samples had been collected and stored within the Biobank of the IRCCS Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy, immediately after getting informed consent, as approved by the regional ethics committee (approval No. 26/ 2014). The study was approved by the neighborhood ethics committee (approval No. 03/2015). Animal breeding and handling had been performed following a protocol authorized by the Animal Care and Use Committee of your University of Verona (CIRSAL), and authorized by the Italian Ministry of Health, in strict adherence towards the European Communities Council directives (86/609/EEC). Consent for publication Not applicable. Competing interests SB is co-founder from the spin-off corporation from the University of Luxembourg Braingineering Technologies s.a.r.l.Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Author information 1 Division of Neurosciences, Biomedicine and Movement Sciences, University of Verona, Strada Le Grazie, 8, 37134 Verona, Italy. 2Molecular Markers Laboratory, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, By way of Pilastroni, 4, 25125 Brescia, Italy. 3Division of Neurology five and Neuropathology, IRCCS Foundation – Carlo Besta Neurological Institute, Through Celoria 11, 20133 Milan, Italy. 4MAC Memory Center, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy. 5Envi.
