The Molecular Scale Program aims to explore whether targeting specific regulators can simultaneously enhance mitochondrial function and suppress Tau aggregation. It adopts a proteomic approach to map the differential vulnerability of the neuronal proteome to misfolding and aggregation following energy stress or the expression of proteins with familial Alzheimer’s mutations. Additionally, the program seeks to provide the first description of the role of wild-type and pathological Tau in controlling NMDR trafficking in synaptic plasticity, offering a mechanistic basis for Tau-based therapeutic development. By applying machine-learning approaches to Alzheimer’s patient-derived neurons, the program aims to determine the mitochondrial components that drive Alzheimer’s pathogenesis. Furthermore, it will pre-clinically test combination therapies targeting signalling pathways involved in protein aggregation in Alzheimer’s.