Abstract
Alois Alzheimer is known for the clinical diagnosis and neuropathological analysis of the neurodegenerative disease named after him. Yet, a less celebrated but equally fundamental contribution lies in his monograph, “Contributions to the knowledge of the pathologic neuroglia and their relationship to degenerative processes in the nervous tissue.” This work, now translated, meticulously details the dynamic role of glial cells in brain pathology, a paradigm-shifting concept for its time. Alzheimer applied then-novel staining techniques -including adaptations of Scharlach red and Mallory hematoxylin- to visualize lipids and protoplasmic degradation in post-mortem human brains. These approaches revealed striking changes in the glial network across disorders ranging from stroke and trauma to multiple sclerosis, syphilis-related dementia, various forms of neurodegeneration, and schizophrenia. He documented the appearance of two novel glial forms, which he termed “ameboid glia” and “glial granule cells”, involved in the phagocytosis of “fatty matter” and “lipoid substances” from degenerating nervous tissue. He also documented “neuronophagia,” where glial cells appeared to directly interact with and “dissolve” damaged neurons. This work laid the conceptual groundwork for modern neuroscience. We now recognize Alzheimer’s “ameboid glia” as the earliest documented observations of activated microglia and astrocytes, and his descriptions of glia’s engagement with cellular damage provided the first evidence for what we now call neuroinflammation. His methodical approach and detailed observations proved that glial cells are not passive bystanders but central, active players that sense, respond to, and shape the course of brain diseases. The English translation and the original German text can be found in the attachment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-026-00933-5.