Fig. 1

Chemical structure of P021 and study design. Female 3 × Tg-AD 3-month-old mice were put on mouse chow (AIN-76, Research Diets, New Brunswick, NJ, USA) that contained 60 nmol P021/g feed. As controls, both 3 × Tg-AD mice and gender-, age-, and genetic background-matched WT mice (129/Sv × C57BL/6) were treated with the vehicle diet. On average the mice consumed ~2.7 g diet/day which amounted to 60 nmol × 2.7 = 162 nmol P021 per mouse per day. At 9, 15, and 18 months posttreatment, mice were sacrificed and their brains studied for expressions and levels of various proteins associated with cognition both immunohistochemically and biochemically (see Figs. 2, 3, 4, 5, 6 and 7). Separate sets of animals were treated as above with a P021 or vehicle diet and tested behaviorally at 9 and 15–16 month posttreatment (Figs. 8 and 9). a The chemical structure of P021. b Study design. 3 × Tg-AD-P021 3 × Tg-AD mice treated with a P021 diet, 3 × Tg-AD-vh 3 × Tg-AD mice treated with a vehicle diet, IHC immunohistochemical staining, WT wild-type control mice