Interestingly, we used ChIP-on-chip, ChIPseq and gene expression data from non-matching cell types and still revealed correlations

as opposed to those ” reactive with Ab specific antibody. This was evident by analysis of the protein aggregation progression by microscopy at different ages. At later time points the difference was less pronounced, but most importantly no decrease in total amount of amyloid deposition was observed as a function of 24735-18-0 curcumin treatment. In this fly model.95% of accumulated Ab142 is insoluble, and a redistribution of soluble/insoluble Ab142 can only be quantified if the soluble fraction was to increase during curcumin treatment. Our data showed that curcumin treatment did not affect the amount or the soluble/insoluble distribution of Ab deposition as quantified by the MSD immunoassay. Furthermore, aged flies expressing the Ab142 peptides in the eyes by a strong driver, analyzed by histological staining in the fluorescence microscope after staining with antibody, the LCO, and the nuclear marker DAPI, also displayed indifferent amyloid deposition patterns upon curcumin treatment. Taken together, in neither of our experiments did we observe any decrease in the amount of Ab or Tau deposition following curcumin treatment. One striking finding in this study was the hyper spectral analysis of p-FTAA fluorescence over time performed on double insert Ab142 expressing flies: curcumin treatment accelerated the formation of well ordered amyloid fibrils in middle age. The notion that curcumin accelerated conformational conversion, rather than modulating the levels of Ab, was hence supported by the quantification of similar amounts of Ab in both treated and untreated brains. Our observations support recent findings in transgenic AD mouse models and in vitro experiments, where it has been suggested that curcumin modulates the Ab amyloid cascade by accelerating fibril formation and decreasing oligomer formation. Fibrillation assays of recombinant Ab142 peptide in absence and presence of curcumin was performed in order to verify such activity of the curcumin used in our Drosophila assay. The in vitro fibrillation assays of recombinant Ab142 peptide in our study hence confirmed the few previous reports that curcumin decrease the population of soluble oligomers and appeared to accelerate formation of large amyloid fibrils in contrast to the majority of reports stating the fibrillation inhibitory mechanism for curcumin. The Arctic mutant peptide Ab142 E22G is well established to form soluble oligomeric protofibrils with high cytotoxicity, and is likely the reason for its strong toxicity in Drosophila. The finding that sub-stoichiometric amounts of curcumin stabilize nucleation of fibril formation in vitro correlates very well with the notion that reduced oligomerization and increased fibril formation in the presence of curcumin markedly protects the Ab142 E22G expressing flies. Our findings in the fly correlates well with those previously reported using mutagenesis where one additional mutation Ab142 I31E in the context of Ab142 E22G, mitigated neurotoxicity in Drosophila by enhancement of amyloid fibril conversion at the expense of oligomers. The same mechanism could explain the neuroprotective effect of curcumin seen for the wild type Ab expressing flies. Concluding remarks and outlook Expressing Ab in the Drosophila CNS results in 11704975” a significant neurotoxic effect, in contrast to that observed in mouse models of AD, which indicates the potency of these models for pharmacological treatment studies.We have demonstrated that curcumin exerts a general neuroprotect