In this study the authors tested the efficacy of apomorphine (APO), a non-specific dopamine agonist, in the 3xTg mouse model. Six-month-old 3xTg mice were treated with subcutaneous injections of APO once a week for 1 month. Memory function was evaluated by Morris water maze before and after the treatment. Brain tissues were examined by immunohistochemical staining and Western blotting. After APO treatment, dramatic improvement in memory function and decreases in Abeta and p-tau pathology were observed.The authors did not find positive immunoreactivity of the dopamine D1–D4 receptors on neurons in the cortices and hippocampi of 3xTg-AD mice and found no improvement of memory function after the injection of pramipexole, another dopamine agonist. Thus, the effects of APO may be mediated, at least in part, by some dopamine-independent pathways. Identification of novel pathways or receptors that mediate the therapeutic effects of APO may contribute to the development of a novel drug for AD.