A secreted form of the beta-amyloid precursor protein (sAPP695) improves spatial recognition memory in OF1 mice

Abstract

The beta-amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD) and appears to be a multifunctional protein. Secreted forms of APP (sAPP) have memory-enhancing effects in certain behavioral paradigms. To investigate sAPP's role in spatial memory processes, we adapted a spatial recognition task and evaluated (1) the performance of OF1 mice after massed training (single 15-min acquisition session) and distributed training (three 5-min acquisition sessions), (2) the decline of spatial recognition performance by introducing different delays (5min, 1, 3, and 24h) between the acquisition and retention phases, and (3) the effects of sAPP(695) on spatial recognition memory. In the present study, mice selectively reacted to a change in the spatial configuration of five objects. Indeed, 3min post-acquisition, mice performed similarly in the massed and distributed versions of the task, by re-exploring the two displaced objects only, whereas mice exposed to the same spatial configuration did not. Additionally, all mice did react to a novel object in a subsequent object recognition phase. Mice detected object displacements 5min, 1h, or 3h post-acquisition, but no more at a 24h-delay. Finally, mice treated with sAPP(695) intracerebroventricularly at a dose of 0.5pg/4microL/mouse, 20-min pre-acquisition or 5-min post-acquisition, still reacted to a spatial change in objects position 24h post-acquisition, in marked contrast to NaCl-treated mice. Our data demonstrate that sAPP(695) significantly improves a form of spatial memory, and confirms the hypothesis of an action of this protein on early memory processes.