The MEMOSAD consortium will present new data at a pre-conference satellite symposium of AD/PD in Barcelona, Spain, in the morning of March 9, 2011 (for further details and registration click on NEWS).

The MEMOSAD periodic report covering the first 18 months of the project has been approved by the Commission. See download "Publishable Summary" 

INTRODUCTION

The project aims at defining the molecular mechanisms of Abeta- and Tau-induced synaptotoxicity and at developing disease-modifying therapeutics for the prevention of  memory loss in Alzheimer disease. This disease, an incurable brain disorder and the major contributor to dementia, is characterized by insoluble aggregates in the brain of affected individuals formed by A-beta peptides and the microtubule-binding protein Tau. Recent data suggest that Abeta aggregation precedes and triggers Tau pathology. One of the early and characteristic symptoms in AD is memory loss. Several lines of evidence suggest that the onset of memory decline does not require neuronal loss, is independent of plaques and tangles and is due to subtle and transient changes at the level of synapses. The toxic Abeta and Tau species that cause synaptic dysfunction, their mechanism of toxicity and the link between both pathologies remain largely unknown. We will employ primary neuronal cultures and animal models (C. elegans, zebrafish and mouse) to define the pathologic pathways leading from Abeta through Tau to synaptotoxicity. In a first set of experiments, we will investigate the effect of defined Abeta species on long term potentiation, synaptic morphology, gene expression, Tau phosphorylation and aggregation, axonal transport and behaviour. Similarly, we will investigate the functional consequences of Tau misfunction, aggregation, hyperphosphorylation and missorting in various cell culture systems (retinal ganglion cells, primary hippocampal neurons, organotypical slices) and animal models, especially with regard to intraneuronal traffic and synaptic function. Once the toxic Abeta and Tau species and their mechanism of toxicity are defined, we will investigate how these pathways interact. Unravelling the pathologic pathways that lead from Abeta through Tau to synaptotoxicity and memory loss should reveal novel points for therapeutic intervention. 

The European Commission will fund the 3-year research project, which started on January 1, 2008, with a maximum of 2,996 million Euro.


For more information see the project info sheet available for download.