Animals

The study utilized female ob/ob mice (B6.Cg-Lep^ob/J) and lean control mice (C57BL/6J) purchased from Jackson Laboratory (Bar Harbor, ME, USA) at five weeks of age. Ob/ob mice display severe obesity and insulin resistance as a result of a spontaneous mutation of the leptin receptor gene. Although this mutation rarely causes diabetes,20 a feature of this model of leptin deficiency is the hyperphagia exhibited by mice and the gradual onset of diabetes, producing a phenotype similar to human patients with T2DM. Female mice were selected since AD is more prevalent in the female population.21 As a phytoestrogen that mimics estrogen, genistein may have more protective effects in the brain of female mice. All mice were housed in an animal facility maintained at a room temperature of 22°C with a 12-hour light/dark cycle and consumed food and water ad libitum. Body weight was measured weekly and the general health was monitored weekly during the study. This study was approved by the Institutional Animal Care and Use Committee at Midwestern University, and carefully followed the National Institutes of Health’s Guide for the Care and Use of Laboratory Animals.