Secreted amyloid precursor protein-alpha can restore novel object location memory and hippocampal LTP in aged rats

Secreted amyloid precursor protein-a (sAPP alpha) is a neurotrophic and neuroprotective molecule which can enhance learning and synaptic plasticity. Aging is associated with memory decline and impaired long-term potentiation (LTP). SAPP alpha therefore has potential as a nootropic agent which could be used to offset age-related cognitive decline. In this study we investigated the effects of sAPPa on spatial memory tasks and LTP in aged and young Long-Evans rats. Two hippocampus-dependent tasks were employed to measure spatial memory that is susceptible to impairments during aging. Aged rats showed a mild deficit in the novel object location task, but memory was significantly enhanced by bilateral intrahippocampal injections of sAPPa. There was no effect on the performance of young animals. In the watermaze task, however, sAPPa did not alleviate age-related decline in spatial memory. In subsequent electrophysiological experiments, LTP was impaired in slices from aged animals, but plasticity was rescued in a concentration-dependent manner by exogenous sAPPa administration. In contrast, LTP was impaired in young animals by sAPPa. Overall, these data support the hypothesis that sAPPa has therapeutic potential as a treatment for age-related cognitive decline. (C) 2016 Elsevier Inc. All rights reserved.