As with AD, there are no effective prevention or treatment strategies for these selleck chemical disorders. Therefore, devel opment of any safe secretase sparing anti Ab drug would have wider clinical applications. It is also important to note that there is a strong rela tionship between cancer and AD. For instance, a recent population based cohort study revealed a 43% lower risk of ever developing AD among cancer patients. Simi larly, patients diagnosed with AD showed a 69% lower risk of developing cancer. These observations have been confirmed by longitudinal prospective studies. Because of the solid relationship between AD and cancer, we speculated that anticancer drugs may exert favorable effects on AD. Therefore, we decided to screen all FDA approved oncology drugs in a cell based assay and identi fied bis chloroethylnitrosourea as a potential anti Ab drug.

Inhibitors,Modulators,Libraries Here we show for the first time that BCNU exposed Chinese hamster ovary cells have significantly reduced levels of amyloid b peptide and c terminal fragments in cell cultures. Also, chronic adminis tration of BCNU for 60 days in a mouse model of AD robustly decreased levels of Ab40 and amyloid plaque burden at six months of age. More importantly, Ab levels and plaque burden were reduced at non toxic concentrations of BCNU independent of secretases sug gesting that BCNU may be an effective Ab lowering, dis ease modifying drug against AD. Methods Chemicals and antibodies The FDA approved oncology drug set II Inhibitors,Modulators,Libraries was obtained from the open chemical repository of the National Cancer InstituteNational Institutes of Health Developmental Therapeutics Program.

1, 3 bis 1 nitrosourea or carmustine, thioflavin S, ethylene glycol Inhibitors,Modulators,Libraries tetraace tic acid, paraformaldehyde, dimethyl sulfoxide and glutaraldehyde were all purchased from Sigma Aldrich. EZ Link Sulfo NHS LC biotin was from Pierce. The monoclonal antibody Ab9 used for immunoprecipitation of Ab was purified from supernatants of the hybridoma generated in mice by Biomatik Corporation. The polyclonal antibody CT15 and the polyclonal antibody, Inhibitors,Modulators,Libraries 63G have been described pre viously. The monoclonal antibody 6E10 was obtained from Covance Inhibitors,Modulators,Libraries Research. Polyclonal anti sAPPb WT antibody was purchased from IBL Co. Ltd. Monoclonal anti Iba1 AIF1 antibody was purchased from Milli pore. Polyclonal anti TGF beta 1 antibody was purchased from Novus Biologicals.

Mouse monoclonal anti body against beta actin was purchased from Genscript USA Inc. Second ary antibodies, such as peroxidase conjugated AffiniPure goat anti mouse and ant rabbit immunoglobulin Gs, were purchased from Jackson ImmunoResearch Laboratories. Anti mouse IgG and anti rabbit IgG agarose beads were from American Qualex Interna tional. ADAM10 and 17 enzymes, Vismodegib msds and the substrate for inhibition assays were pur chased from R D Systems.