Although Alzheimer’s disease has a major societal impact and cost in our aging societies, very little progress has been made from a therapeutic point of view, despite major efforts in clinical research. This apparent paradox may stem from a still partial understanding of the molecular mechanisms that lead to this neurodegenerative pathology. Thus, it now seems obvious to consider Alzheimer’s disease not only under its aggregative aspect, but to consider it under a multifactorial aspect.

We will try to shed some original light on the subject by focusing on an alteration in the homeostasis of metals in the brain, which potentially promotes neuronal degeneration. Among these metals, copper, whose level could be reduced in neurons, binds to amyloid beta and is also capable of catalyzing the production of reactive oxygen species toxic to neurons.

We seek to better understand the role of deregulated brain copper levels in the development of Alzheimer’s disease, focusing on neuronal function. The use of novel copper sensors and shuttles capable of capturing copper from amyloid plaques and delivering it to neurons represent valuable tools to better understand the implications of deregulated copper homeostasis and have potential applications in restoring copper homeostasis in Alzheimer’s disease. In parallel, we are studying the potential synergistic role of excess amylin release in diabetic patients who have a 2-3 fold increased risk of developing Alzheimer’s disease.