Various previous studies have shown that different neurodegenerative disorders differentially affect different brain regions. Here, we propose to use magnetic resonance imaging (MRI) to identify multi-modal imaging signatures of either brain regional susceptibility or resistance to neurodegeneration. Our main current approach to tackle this question is based on the assessement of ante-mortem MRI acquisitions that also have post-mortem MRI neuropathology diagnosis. We have already identified that primary age-related tauopathy (PART) atrophy patterns differ from Alzheimer’s disease and we are now exploring the potential mechanisms, and other associated phenotypes, that differentiate these pathological conditions. Importantly, this knowledge can pave the way for precision-medicine applications in the context of neurodegenerative disorders.