Nevertheless, transgenic mice are a slow and expensive model for the screening and the evaluation of new molecules. Moreover, they are not highly predictive because AD is mainly an aging disease, not related to genetic disorders and also because none of these transgenic mice fully recapitulates the AD pathology. Due to the lack of a fast and predictive animal model, many drug-candidates failed in phases II or III of human clinical trials. A survey of the literature suggested that in rodents, the amyloid – related neuropathological features of AD might be mimicked by intra-cerebroventricular or intra-cerebral injections of Ab peptides of different lengths, whereas systemic inoculation yielded no detectable induction of cerebral amyloidosis in APP23 transgenic mice. Although various attempts were realized with peptides of different length, in the mouse, most of the studies using the Ab1–42 human peptide showed impaired cognitive functions early after icv injection. These studies suggested also that the effects the Ab1–42 peptide could be induced after a single icv injection. For instance, it has been shown that between 1 and 29 days after a single icv Ab1–42 injection, mice displayed impaired performances in passive avoidance, alternation behavior and spatial learning along with a decrease in acetylcholine levels in the cortex and an increase of immunoreactivities of the astrocyte marker GFAP and of interleukine-1b in the hippocampus. The proposal that small soluble oligomers in the aggregation process confer synaptic dysfunction whereas large, insoluble deposits might function as reservoirs of the bioactive oligomers could account for this fast loss of episodic memory after a single icv injection of small amyloids. Recent studies confirmed that Ab1–42 are prone to highly aggregate as plaques and to penetrate neurons as oligomers and activate p53, enhancing neuronal apoptosis. Therefore we decided to develop a « fast murine screening model » by using of non-transgenic mice suffering from cognitive deficits induced by the intracerebroventricular injection of Ab1–42 oligomers that are considered as a causative agent in AD associated with oxidative stress and aging. Episodic memory deficits are a prominent feature of AD. In the present study, these deficits were assessed in control and treated mice, using a well-validated and automated learning procedure, contextual fear conditioning, that requires intact declarative memory that is affected in Staurosporine early-stage AD patients, and presents valuable methodological advantages including intrinsic validity and reliability. The results of the present study clearly show that a single icv injection of Ab1–42 oligomers generates episodic-like memory deficits in mice after a 21-day delay. The presence of small amounts of that amyloid peptide under its pathogenic form in the brain of adult mice induced memory impairments ascribable to defective consolidation or defective recall of an episodic representation. Therefore, our results suggest that deleterious effects of the Ab1–42 peptide could impair the functioning of the hippocampal structure, reflecting typical features of human memory deficits observed in AD, and thus establishing the validity of this murine model of amyloid pathology. As working hypothesis, one can consider that the injection of the pathogenic Ab1–42 peptide is disturbing the copper circulation by trapping a large amount of copper ions, and, as a consequence, is creating probably a deficit of copper for metalloenzymes that need this cation as essential element of their active sites. Because of its high affinity for copper ions, PA1637 is probably able to extract these ions from amyloid peptides.