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Objective Alzheimers disease (AD) is characterized clinically by progressive memory impairment and pathologically by senile plaques composed of amyloid β peptide (Aβ).Our previous studies indicated that Humanin (HN), originally identified from an occipital lobe of an AD patient, abolishes neuronal celt death induced by Aβ.Colivelin (CLN), the strongest HN derivative so far developed, is a fusion peptide composed of a potent HN derivative named AGA-(C8R)HNG17 attached to the C terminus of activity dependent neurotrophic factor (ADNF).The present studies, for the first time, investigated the neuroprotective effects of CLN against Aβ-induced impairments of synaptic palasticity and spatial memory.Methods The in vivo hippocampal long term potentiation (LTP) of field excitatory postsynaptic potential (fEPSP) was induced by delivering tetanic stimuli to the CA1 region.The spatial learning and memory behavior of rats was tested by using a Morris water maze.Results (1) Hippocampal injection of Aβ25-35 (2 nmol) surppressed magnitude of LTP induced by high frequency stimulation (HFS), reduced the maintenance time of LTP and impaired spatial memory of rats, with a prolonged latency was in morris water maze; (2) CLN delivered alone, even at a high concentration (0.2 nmol), did not show any significant effect on LTP and spatial memory of rats; (3) In co-application group (CLN + Aβ25-35), the Aβ (2 nmol) induced impairment of LTP and memory behavior was significantly ameliorated by pretreatment with different concentrations of CLN, even at a very low concentration (2 pmol).Conclusion CLN could ameliorate LTP suppression and memory impairment induced by Aβ suggesting that CLN might be a promissing therapeutic chemical in the prevention and treatment of AD.