We report a qualitative study on central nervous system (CNS) damage that demonstrates the ability of X-ray phase contrast tomography (XPCT) to confirm data obtained with standard 2D methodology and permits the description of additional features that are not detected with 2D or other 3D techniques. In contrast to magnetic resonance or computed tomography, XPCT makes possible the high-resolution 3D imaging of soft tissues classically considered "invisible" to X-rays without the use of additional contrast agents, or without the need for intense processing of the tissue required by 2D techniques. Most importantly for studies of CNS diseases, XPCT enables a concomitant multi-scale 3D biomedical imaging of neuronal and vascular networks ranging from cells through to the CNS as a whole. In the last years, we have used XPCT to investigate neurodegenerative diseases, such as Alzheimer’s disease (AD) and multiple sclerosis (MS), to shed light on brain damage and extend the observations obtained with standard techniques. Here, we show the cutting-edge ability of XPCT to highlight in 3D, concomitantly, vascular occlusions and damages, close associations between plaques and damaged vessels, as well as dramatic changes induced at neuropathological level by treatment in AD mice. We corroborate data on the well-known blood-brain barrier dysfunction in the animal model of MS, experimental autoimmune encephalomyelitis, and further show its extent throughout the CNS axis and at the level of the single vessel/capillary.