Since Alzheimer’s Disease (AD) has a strong genetic component, knowledge of this genetic component would help identify relevant signalling pathways. We have been able to characterize genetic factors and the combination of this information with biological data has revealed that the synaptic loss observed early in the disease progression may be genetically driven. The objective of this project is thus to evaluate this hypothesis: (i) To systematically identify which genetic determinants of AD are involved at the synapses (ii) To define AD genetic risk factors involved in synaptic density as modulators/mediators of Aß/Tau synaptic toxicity. (iii) To further characterise the physiological and pathophysiological roles of the genetic risk factors in synaptic function and plasticity. If this hypothesis is correct, this work could lead to a better understanding of the pathophysiological processes of AD and open up new therapeutic approaches targeting an early event of AD, synaptic loss.