Neurodegenerative diseases, such as Alzheimer's and Parkinson's, are considered prion-like disorders because they are all proteinopathies in which aberrant proteins spread throughout the brain during disease progression. The overall aim of this study is to determine how glial cells are commonly involved in the neurodegeneration progress observed in all these pathologies. The suggestion that they are cell types in which prion and prion-like disorders have common behaviour is the hypothesis on which this study is based. Morphological and distribution differences in astroglial and microglial cells in the cerebellum from prion and prion-like disease-affected patients were assessed here by histopathological and immunochemical tools. To our knowledge, this is the first study to focus on the comparative assessment of glial profiles in these human brains. Activated microglial population was demonstrated in both, prion and prion-like disorders, although in higher extent in the first. In astroglial activation, specific patterns of alterations suggesting both degenerative and potentially neuroprotective or restorative stem cell response, were shown to be alternatively shared by cerebella from all disorders studied. Neuro-protective strategies for these disabling disorders are particularly desirable. Copyright © 2019 Elsevier B.V. All rights reserved.