# The functional role of glial cells in the pathologic brain as reviewed by Alois Alzheimer in 1910

**Authors:** Helmut Kettenmann, Hans Lassmann, Bilge Ugursu, Xianyuan Xiang

PMC · DOI: 10.1186/s13024-026-00933-5 · Molecular Neurodegeneration · 2026-02-13

## TL;DR

Alois Alzheimer's 1910 work revealed that glial cells actively respond to brain diseases, laying the foundation for modern understanding of neuroinflammation.

## Contribution

The paper highlights Alzheimer's pioneering observations of glial cell activity in brain pathology, including early descriptions of microglia and astrocyte activation.

## Key findings

- Alzheimer described 'ameboid glia' and 'glial granule cells' as active participants in clearing fatty matter from degenerating tissue.
- He documented 'neuronophagia,' where glial cells interact with and dissolve damaged neurons.
- His work established that glial cells are central, active players in brain diseases, not passive bystanders.

## 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.

The online version contains supplementary material available at 10.1186/s13024-026-00933-5.

## Linked entities

- **Diseases:** stroke (MONDO:0005098), trauma (MONDO:0021178), multiple sclerosis (MONDO:0005301), schizophrenia (MONDO:0005090)

## Full-text entities

- **Genes:** TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, TREM2 (triggering receptor expressed on myeloid cells 2) [NCBI Gene 54209] {aka AD17, PLOSL2, TREM-2, Trem2a, Trem2b, Trem2c}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, APOE (apolipoprotein E) [NCBI Gene 348] {aka AD2, APO-E, ApoE4, LDLCQ5, LPG}
- **Diseases:** cysts (MESH:D003560), Epileptics (MESH:D004827), proteinopathy (MESH:D057165), brain diseases (MESH:D001927), delirium (MESH:D003693), tissue (MESH:D017695), paralysis (MESH:D010243), multiple sclerosis (MESH:D009103), astrogliosis (MESH:D005911), meningoencephalitis (MESH:D008590), stroke (MESH:D020521), schizophrenia (MESH:D012559), oligodendrocyte degeneration (MESH:D056784), Tay Sachs disease (MESH:D013661), syphilis (MESH:D013587), trauma (MESH:D014947), luetic encephalitis (MESH:D004660), bleeding (MESH:D006470), dementia (MESH:D003704), chorea (MESH:D002819), tuberculous (MESH:D014390), brain trauma (MESH:D000070642), Neurological Diseases (MESH:D020271), nervous system diseases (MESH:D009422), acute multiple sclerosis (MESH:D020529), lysosomal storage diseases (MESH:D016464), vascular diseases (MESH:D014652), CNS damage (MESH:D002493), seizures (MESH:D012640), neurodegeneration (MESH:D019636), inflammation (MESH:D007249), neuronal dysfunction (MESH:D009461), fatty (MESH:D008067), LDAM (MESH:D011017), infectious (MESH:D003141), heart failure (MESH:D006333), psychosis (MESH:D011618), cognitive decline (MESH:D003072), neurotoxic (MESH:D020258), neurological and psychiatric diseases (MESH:D001523), Alzheimer (MESH:D000544), metabolic disturbances (MESH:D024821), neuroinflammation (MESH:D000090862), brain damage (MESH:D001925)
- **Chemicals:** fatty acids (MESH:D005227), glutamate (MESH:D018698), acetylcholine (MESH:D000109), toluidine (MESH:D014052), ROS (MESH:D017382), cholesterol (MESH:D002784), Mallory (-), NO (MESH:D009569), GABA (MESH:D005680), TCA (MESH:D014238), fuchsin (MESH:D012394), Lipid (MESH:D008055), fat (MESH:D005223), alcohol (MESH:D000438), iron (MESH:D007501), ATP (MESH:D000255), hematoxylin (MESH:D006416)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC13005332/full.md

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC13005332/full.md

## References

2 references — full list in the complete paper: https://tomesphere.com/paper/PMC13005332/full.md

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Source: https://tomesphere.com/paper/PMC13005332