Apicidin attenuates memory deficits by reducing the A beta load in APP/PS1 mice

AimsAmyloid beta (A beta) is an important pathological feature of Alzheimer's disease (AD). A disintegrin and metalloproteinase 10 (ADAM10) can reduce the production of toxic A beta by activating the nonamyloidogenic pathway of amyloid precursor protein (APP). We previously found that apicidin, which is a histone deacetylase (HDAC) inhibitor, can promote the expression of ADAM10 and reduce the production of A beta in vitro. This study was designed to determine the potential of apicidin treatment to reverse learning and memory impairments in an AD mouse model and the possible correlation of these effects with ADAM10. MethodsNine-month-old APP/PS1 mice and C57 mice received intraperitoneal injections of apicidin or vehicle for 2 months. At 11 months of age, we evaluated the memory performance of mice with Morris water maze (MWM) and context fear conditioning tests. The A beta levels were assessed in mouse brain using the immunohistochemical method and ELISA. The expression of corresponding protein involved in proteolytic processing of APP and the phosphorylation of tau were assessed by Western blotting. ResultsApicidin reversed the deficits of spatial reference memory and contextual fear memory, attenuated the formation of A beta-enriched plaques, and decreased the levels of soluble and insoluble A beta 40/42 in APP/PS1 mice. Moreover, apicidin significantly increased the expression of ADAM10, improved the level of sAPP alpha, and reduced the production of sAPP beta, but did not affect the levels of phosphorylated tau in APP/PS1 mice. ConclusionApicidin significantly improves the AD symptoms of APP/PS1 mice by regulating the expression of ADAM10, which may contribute to decreasing the levels of A beta rather than decreasing the phosphorylation of tau.