Goals | The Lesné Laboratory

The major research goal of our laboratory is to understand the molecular and cellular mechanisms triggered by proteins abnormally aggregating in cerebral brain tissues during the course of neurodegenerative disorders, with a specific focus on Alzheimer’s disease. Empowered by this new knowledge, we aim at developing therapeutic strategies to counter the action of these molecules in preclinical models of the disease.

Despite evidence for a pathogenic role of amyloid plaques and associated neuronal dystrophy, it has become apparent in the past decade that soluble, non-fibrillar amyloid-beta (Aβ) assemblies, also called Aβ oligomers, might be more critical than plaque load in the pathogenesis of Alzheimer’s disease-related neuronal dysfunction and memory impairment. However, the toxicity of these relative species and the exact mechanism by which these multimeric forms are able to alter brain and neuronal function remain to be identified. Due to the size of Aβ oligomers and their presence in the extracellular space, our laboratory is examining whether and how Aβ oligomers can interact with neurons at the plasma membranes. Moreover, our group also focuses on examining whether soluble Aβ oligomers could represent the “missing” link between tau and amyloid pathologies in Alzheimer’s disease.

In parallel to our efforts on Aβ oligomers, we started examining the relative contribution of soluble alpha-synuclein (classically linked to Parkinson’s disease) in Alzheimer’s disease-associated cognitive impairment.