CONICET | Buscador de Institutos y Recursos Humanos

Progressive memory loss and cognitive dysfunction are the hallmark clinical features of Alzheimers disease (AD). Moreover, senile plaques containing mainly amyloid-β (Aβ) peptides, neurofibrillary tangles composed of hyperphosphorylated tau (τ), and neuronal loss are the major features of AD. However, Aβ are elevated without plaque formation or nerve cell loss, yet learning and memory deficits are evident in early stages of AD. Identifying the molecular triggers for the onset of AD-related cognitive decline presently requires the use of suitable animal models, such as the triple transgenic mouse model of AD (3xTg-AD), which develops both amyloid and tangle pathology. Here we characterize the onset of learning and memory deficits in these transgenic mice, in addition to determining different molecular markers that correlate. Impaired performance was seen at different ages (4 6 months) in the transgenic mice in the Novel Object Recognition task (NOR). Furthermore, molecular markers (phosphoERK, calcineurin and Nuclear Factor kappa B) were determined at 3 and 6 months in hippocampus and cortex, in order to establish potential early markers that likely correlate with the memory impairment observed. Taken together, our results will contribute to elucidate molecular pathways that early dysregulate and are partially responsible for the mild cognitive impairments observed in early stages of AD.