The identity and function of microglia in neurodegeneration
Abstract
The predominant type of immune cell in the brain is the microglia, a type of tissue-resident macrophage. In a variety of neurodegenerative settings, microglia alter their transcriptional profile, morphology and function in similar ways; thus, these activated cells have been called 'degeneration- or disease-associated microglia' (DAM). These activated microglia can perform different functions and exert both positive effects and negative effects in different mouse disease models. In humans, mutations in genes expressed in microglia are linked to various neurodegenerative diseases. Here we provide an overview of the common microglial response to neurodegeneration and key contributing pathways; delineate the multifaceted functions of activated microglia spanning various diseases; and discuss insights from the study of human disease-associated genes. We argue that strong evidence from both mouse models and human genetics causally links the function of activated microglia to neurodegeneration.
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DAM phenotype has been proposed to represent a universal and intrinsic microglial response program to CNS disease, retained across neurodegenerative and non-neurodegenerative diseases.
“The DAM phenotype has been proposed to represent a universal and intrinsic microglial response program to CNS disease, since it appears to be retained across a number of neurodegenerative and non-neurodegenerative diseases [74, 291]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [291]
DAM-expressed factors such as apolipoprotein, CSF1, and secreted phosphoprotein 1 act as autocrine ligands on DAM-expressed receptors, sustaining and perpetuating neurodegenerative phenotype.
“DAM-expressed factors, such as apolipoprotein, colony-stimulating factor 1 (CSF1) and secreted phosphoprotein 1, act as autocrine ligands on DAM-expressed receptors, together sustaining and perpetuating the neurodegenerative phenotype [291]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [291]
Complement activation can exacerbate synaptic loss and contribute to memory loss and cognitive decline.
“complement activation, which is important for microglial phagocytosis, can exacerbate synaptic loss [152, 284, 291] and contribute to memory loss and cognitive decline [75]”
From Microglia and monocytes in inflammatory CNS disease: integrating phenotype and function (2022) · cites this paper as [291]
Microglia are classified into M1 (classically activated) cells that secrete proinflammatory cytokines and M2 (alternatively activated) cells that promote tissue regeneration and repair.
“Microglia are classified into two subtypes: classically activated (M1) cells, which secrete proinflammatory cytokines, and alternatively activated (M2) cells, which promote tissue regeneration and repair [9–12].”
From Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression (2022) · cites this paper as [11]
Microgliosis is a known feature of AD.
“Microgliosis is a known feature of AD [reviewed in (92, 93)]”
From The Transcriptional Landscape of Microglial Genes in Aging and Neurodegenerative Disease (2019) · cites this paper as [92]
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“Furthermore, complement activation, which is important for microglial phagocytosis, can exacerbate synaptic loss [152, 284, 291] and contribute to memory loss and cognitive decline [75] (Table 5).”
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Self-citation
- Authors
- Song, W. M., & Colonna, M.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Colonna, Marco
- Venue
- Nature Immunology
- Published
- 2018-09-24
- Volume
- 19
- Issue
- 10
- Pages
- 1048-1058
- ISSN
- 1529-2908 (ISSN-L)
- 1529-2916
- OpenAlex
- W2891888347
- Semantic Scholar
- 56fd070c6693804f7ada07ce3ee33529dfa55dbf
- Cited by
- 308
- References
- 178
- Citations by year
- 2026: 21 · 2025: 28 · 2024: 37 · 2023: 49 · 2022: 53 · 2021: 42 · 2020: 42 · 2019: 33 · 2018: 3
- FWCI
- 2.84
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
- Keywords
- microglia, neurodegeneration, disease-associated microglia, microglial activation, tissue-resident macrophages, microglial morphology, neurodegenerative disease models, microglial function
- MeSH terms
- Animals, Humans, Microglia, Neurodegenerative Diseases
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