This index page provides a comprehensive overview of the different activation states of microglia, the resident immune cells of the central nervous system. Microglia adopt various phenotypic states in response to pathological stimuli, and understanding these states is crucial for developing therapeutic interventions for neurodegenerative diseases. [1]
The baseline state of microglia in a healthy brain. These cells continuously survey their environment and respond to disturbances. [2]
The pro-inflammatory, cytotoxic state induced by IFN-γ and LPS exposure. [3]
The anti-inflammatory, tissue repair state. Further subdivided into M2a, M2b, and M2c. [4]
A specialized microglia phenotype associated with neurodegenerative diseases.
A transitional state between homeostatic and DAM, characterized by unique lipid metabolism changes.
Microglia specifically responding to amyloid pathology, distinct from classical DAM.
Microglia that have accumulated large amounts of lipid droplets, often seen in aging and AD.
Microglia with iron accumulation, associated with aging and neurodegenerative processes.
Age-related changes in microglia that promote chronic inflammation and reduced function.
| Gene/Protein | Role | Disease Relevance |
|---|---|---|
| TREM2 | Triggering receptor on myeloid cells 2 | AD risk factor |
| TYROBP | TYROBP signaling adaptor | DAM signaling |
| APOE | Apolipoprotein E | Lipid transport, AD risk |
| CD33 | Siglec receptor | AD risk factor |
| CX3CR1 | Fractalkine receptor | Neuroprotection |
| P2RY12 | P2Y12 receptor | Homeostatic marker |
| Therapeutic Approach | Target State | Mechanism |
|---|---|---|
| TREM2 agonists | DAM | Enhance phagocytosis |
| CSF1R inhibitors | M1, DAM | Reduce neuroinflammation |
| CD33 inhibitors | M1 | Reduce inflammation |
| NLRP3 inhibitors | M1 | Inflammasome blockade |
Keren-Shaul et al. A Unique Microglia Type Associated with Alzheimer's Disease (2017). 2017. ↩︎
Deczkowska et al. Disease-Associated Microglia: A Universal Memory Cell (2018). 2018. ↩︎
Hansen et al. TREM2 and Neurodegeneration (2018). 2018. ↩︎
Mosher & Wyss-Coray, Microglial Dysfunction in Alzheimer's Disease (2014). 2014. ↩︎