Our work in the last years has been centered in the analysis of molecular changes associated to synaptic plasticity deficits related to Alzheimer’s Disease (AD), in particular, aspects related to learning and memory. These processes are accompanied by persistent adaptive changes that lead to a reinforcement of the interneuronal communication by new synapse formation or reinforcement of the already existing ones.

Considering that the early phases of AD are characterized by a synaptic dysfunction, particularly of excitatory type, a dysfunction manifested long before the appearance of plaque deposits or neuronal loss that is correlated with the cognitive impairment, our group has been focused at the analysis of  adaptive molecular changes associated to learning and memory processes in transgenic mice that overexpress  human APP. This work is aimed at studying different aspects directly related to synaptic remodeling and increase of interneuronal communication. We use transgenic mice J20 that express human APP with the Swedish (K670N/M671L) and Indiana (V717F) mutations (hAPPSwe/Ind), and mice of the I5 line that express the nonmutated form of this protein. We have started the characterization of the cognitive state of these animals by using the object recognition test  and the Morris water maze, detecting an early learning impairment that is correlated with specific synaptic alterations, related to the excitatory transmission. In some cases these findings are not related to the presence of elevated β-amyloid levels, and other non-amyloidogenic products derived from APP processing also seem to have a role in the synaptic dysfunction and memory impairment (Schiapparelli et al, submitted).

Our present interests are centered in the analysis of synaptic alterations related to the cognitive decline in these animals in normal conditions and after the induction of memory processes. Particularly, the work is oriented to the temporary study of alterations in the glutamatergic transmission, affecting the synaptic redistribution of AMPA receptors, and modifications of proteins implicated in the dendritic remodeling, efrin/Eph system and the signaling pathway (family of  Rho proteins and effectors) as well as alterations of the neuronal cytoskeleton. Recent data from our group (Simón et al., 2008) have shown the existence of early alterations in the ephrin/Eph system before the cognitive impairment in these transgenic animals modelling Alzheimer’s disease.

Our research group is part of the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Ciberned represents the Spanish initiative to combat neurodegenerative diseases.  CIBERNED is a “networked” institute that brings together the best basic and clinical neuroscience research groups.  Its objective is to foster high-quality, co-operative medical research aimed at the prevention and treatment of neurodegeneration.