We aim to understand how neuronal trafficking dysfunction underlie synapse loss during aging, potentiating Alzheimer's disease (AD).
We are currently investigating the pathogenicity of endosomal genetic risk factors associated with late-onset Alzheimer's disease and how neuronal aging impacts endocytosis of AD-related proteins and lysosomal function.
We rely on advanced quantitative microscopy, from live-cell Imaging to super-resolution, to perform mechanistic studies using cultures of primary mouse cortical neurons, neuronal cell lines, human neurons derived from hIPSCs and aged mice. We are introducing patients' mutations into healthy neurons using gene-editing techniques to model late-onset AD.
Our goal is to uncover druggable molecular mechanisms that underlie synapse dysfunction early on in a still reversible cellular phase of neurodegeneration. Moreover, we are establishing neuronal models that recapitulate late-onset AD early cytopathology.