In this study the authors performed a preclinical evaluation of the TrkB agonist 7,8-DHF in the 5xFAD mouse model of AD. Results showed that 7,8-DHF rescued memory deficits of Tg mice in the spontaneous alternation Y-maze task. In addition, 7,8-DHF restored deficient TrkB signaling inTg mice without affecting endogenous BDNF levels. Treatment Tg mice with 7,8-DHF also blocked BACE1 elevations and lowered levels of the beta-secretase cleaved C-terminal fragment of amyloid precursor protein (C99), Abeta 40, and Abeta 42 in brain Treatment of non-transgenic mice with 7,8-DHF was associated with decreased BACE1 expression, suggesting that BDNF-TrkB signaling is also important for down regulating baseline levels of BACE1. Together, the findings suggest that TrkB activation with a 7,8-DHF can ameliorate AD-associated memory deficits, which may be, at least in part, attributable to reductions in BACE1 expression and beta-amyloidogenesis.