Cited by 213Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Microglia in Brain Development, Homeostasis, and Neurodegeneration

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Bohlen, Christopher J., Friedman, Brad A., Dejanovic, Borislav, Sheng, Morgan·2019·Annual Review of Genetics

Abstract

Advances in human genetics have implicated a growing number of genes in neurodegenerative diseases, providing insight into pathological processes. For Alzheimer disease in particular, genome-wide association studies and gene expression studies have emphasized the pathogenic contributions from microglial cells and motivated studies of microglial function/dysfunction. Here, we summarize recent genetic evidence for microglial involvement in neurodegenerative disease with a focus on Alzheimer disease, for which the evidence is most compelling. To provide context for these genetic discoveries, we discuss how microglia influence brain development and homeostasis, how microglial characteristics change in disease, and which microglial activities likely influence the course of neurodegeneration. In all, we aim to synthesize varied aspects of microglial biology and highlight microglia as possible targets for therapeutic interventions in neurodegenerative disease.

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Crossref · 10.1146/annurev-genet-112618-043515

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165 of 165 references verified0 citation errors · 0 not checkable

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  • Microglia constantly eliminate cell debris and dead cells through highly efficient phagocytosis.

    “Microglia constantly eliminate cell debris and dead cells through highly efficient phagocytosis using specific recognition, engulfment, and degradation processes to maintain brain homeostasis in health and disease [310,325,326,327].”

    From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [327]

    The “Microglial Clearance of Apoptotic Cells” section says microglia remove dead cells through phagocytosis and describes receptors involved in that process. The cited passages do not establish that they do so constantly or with the claimed high efficiency, and the passage mentioning cellular debris concerns complement-mediated clearance in the periphery. (LLM, conf=0.82)

    Experimental — accuracy not yet measured
  • Once abnormally reactive in Alzheimer's disease, microglia can promote synaptic and neuronal loss while exacerbating tau proteinopathy.

    “Once abnormally reactive in AD, microglia can promote synaptic and neuronal loss while exacerbating tau proteinopathy11,12.”
  • Genetic risk studies suggest that microglia not only respond to Alzheimer's disease but also modulate its course.

    “Studies of genetic risk for sporadic AD have suggested that microglia not only respond to disease but modulate disease course13.”

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Authors
Bohlen, C. J., Friedman, B. A., Dejanovic, B., & Sheng, M.
Affiliations
Genentech (US)
Venue
Annual Review of Genetics
Published
2019-12-03
Volume
53
Issue
1
Pages
263-288
ISSN
  • 0066-4197 (ISSN-L)
  • 1545-2948
OpenAlex
W2972808567
Cited by
212
References
165
Citations by year
2026: 17 · 2025: 29 · 2024: 53 · 2023: 36 · 2022: 33 · 2021: 26 · 2020: 18
FWCI
1.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Annual Review of Genetics (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
Keywords
microglia, Alzheimer's disease, neurodegeneration, brain development, brain homeostasis, microglial dysfunction, genetic risk factors, genome-wide association study, therapeutic target
MeSH terms
Aging, Alzheimer Disease, Animals, Brain, Central Nervous System, Complement Pathway, Classical, Gene Expression Regulation, Homeostasis, Humans, Macrophages, Transforming Growth Factor beta, Microglia, Neurodegenerative Diseases, Genetic Predisposition to Disease, Plaque, Amyloid

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