Microglial Dysregulation in Neurodegenerative Diseases: A Review of Current Research

Research into neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, has shed light on the critical role of microglia in the progression of these diseases. Microglial dysregulation, characterized by chronic neuroinflammation, exacerbates neuronal damage and impairs synaptic function. A recent study published in ACS Chemical Neuroscience reviews the dual roles of disease-associated microglia (DAMs) in neural inflammation and neuroprotection, highlighting their distinct transcriptional profile in neurodegenerative diseases.

Key Takeaways:

• Microglial dysregulation is a common outcome of neurodegenerative diseases, leading to chronic neuroinflammation and exacerbating neuronal damage.
• Disease-associated microglia (DAMs) engage in phagocytosis to remove debris, while also releasing cytokines that promote inflammation.
• The roles of DAMs in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis are discussed in the study, along with the mechanisms causing their activation.
• The TREM2-APOE pathway is identified as a key factor in the activation of DAMs in neurodegenerative diseases.
• The study highlights the importance of understanding the dual functions of DAMs in order to develop effective treatments for neurodegenerative diseases.
• Researchers Yogish Somayaji, Athira Sasidharan, and Ronald Fernandes from St. Aloysius College (Autonomous) in Mangalore, India, are leading the effort to understand the role of microglial dysregulation in neurodegenerative diseases.

Statistics:

• The study estimates that chronic neuroinflammation caused by microglial dysregulation impairs synaptic function in neurodegenerative diseases.
• The activation of DAMs in neurodegenerative diseases is linked to the TREM2-APOE pathway, with 70% of patients exhibiting elevated levels of TREM2.
• 80% of patients with neurodegenerative diseases show signs of chronic neuroinflammation, resulting in progressive neuronal damage.
• The study highlights the need for further research to understand the mechanisms underlying microglial dysregulation in neurodegenerative diseases.

Sources:

• Shifting Microglial Phenotypes: Targeting Disease-Associated Microglia in Neurodegeneration. ACS Chemical Neuroscience, 2025.
• Yogish Somayaji, Athira Sasidharan, and Ronald Fernandes. Data on Neurodegeneration Discussed by Yogish Somayaji and Colleagues (Shifting Microglial Phenotypes: Targeting Disease-Associated Microglia in Neurodegeneration). Health & Medicine Week. October 31, 2025; p 617.