A little-known tissue composed of a cluster of immune cells could offer novel insights into the development of neurological disorders. Meninges' immune system changes with age and neurodegeneration. Are they protecting the brain or fueling disease? Mapping and analyzing the so-called ectopic lymphoid structures (ELSs) in the meninges at different ages in preclinical models of neurodegenerative diseases such as Alzheimer's may help clarify whether they are good, bad, or ugly, as in the iconic film by Sergio Leone.