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Disease-associated microglia in neurodegenerative diseases: Friend or foe?

Yi-Hsuan Cheng1, Margaret S Ho1,2

  • 1Institute of Neuroscience, National Yang Ming Chiao Tung University, Taipei, Taiwan.

Plos Biology
|October 21, 2025
PubMed

Insights

Disease-associated microglia (DAM) are a conserved cell state found in neurodegenerative diseases like Alzheimer's. Research explores their role in sensing and potentially treating these conditions.

Area of Science:

  • Neuroscience
  • Immunology
  • Genomics

Background:

  • Single-cell transcriptomics reveals disease-associated microglia (DAM), a conserved microglia state implicated in Alzheimer's disease (AD), amyotrophic lateral sclerosis, and aging.
  • DAM exhibit downregulated homeostatic genes and upregulated lipid metabolism and phagocytosis genes, including AD risk factors.

Purpose of the Study:

  • To investigate if DAM function as a universal sensor across various neurodegenerative diseases.
  • To discuss the dynamics, origins, and therapeutic potential of DAM in neurodegeneration.
  • To review evidence for a protective role of DAM in regulating disease processes.

Main Methods:

  • Analysis of single-cell transcriptomic data from neurodegenerative disease models.
  • Review of existing literature on DAM characteristics and functions.
  • Comparative analysis of DAM states across different neurodegenerative conditions.

Main Results:

  • DAM are identified as a conserved microglia state associated with neurodegeneration.
  • DAM exhibit specific gene expression patterns related to lipid metabolism and phagocytosis.
  • The universal role of DAM across all neurodegenerative diseases is still under investigation.

Conclusions:

  • DAM represent a significant cellular response conserved across multiple neurodegenerative diseases.
  • Understanding DAM dynamics and origins offers therapeutic potential for neurodegenerative conditions.
  • Evidence suggests DAM may play a protective role in neurodegeneration.

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