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Cited by 298Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsNeurological Disease Mechanisms and Treatments

Microglia in Alzheimer Disease: Well-Known Targets and New Opportunities

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Hemonnot, Anne-Laure, Hua, Jennifer, Ulmann, Lauriane, Hirbec, Hélène·2019·Frontiers in Aging Neuroscience
DOI 10.3389/fnagi.2019.00233PMC PMC6730262
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Abstract

Microglia are the resident macrophages of the central nervous system. They play key roles in brain development, and physiology during life and aging. Equipped with a variety of molecular sensors and through the various functions they can fulfill, they are critically involved in maintaining the brain's homeostasis. In Alzheimer disease (AD), microglia reaction was initially thought to be incidental and triggered by amyloid deposits and dystrophic neurites. However, recent genome-wide association studies have established that the majority of AD risk loci are found in or near genes that are highly and sometimes uniquely expressed in microglia. This leads to the concept of microglia being critically involved in the early steps of the disease and identified them as important potential therapeutic targets. Whether microglia reaction is beneficial, detrimental or both to AD progression is still unclear and the subject of intense debate. In this review, we are presenting a state-of-knowledge report intended to highlight the variety of microglial functions and pathways shown to be critically involved in AD progression. We first address both the acquisition of new functions and the alteration of their homeostatic roles by reactive microglia. Second, we propose a summary of new important parameters currently emerging in the field that need to be considered to identify relevant microglial targets. Finally, we discuss the many obstacles in designing efficient therapeutic strategies for AD and present innovative technologies that may foster our understanding of microglia roles in the pathology. Ultimately, this work aims to fly over various microglial functions to make a general and reliable report of the current knowledge regarding microglia's involvement in AD and of the new research opportunities in the field.

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  • The interaction of microglia within the complex brain microenvironment of Alzheimer's disease (e.g. neurons, astrocytes and amyloid-β plaques) is still not well explored.

    “Especially, the interaction of microglia within the complex brain microenvironment of AD (e.g. neurons, astrocytes and amyloid-β plaques) is still not well explored.11, 12”

    From Acoustofluidic assembly of 3D neurospheroids to model Alzheimer's disease (2020) · cites this paper as [11]

    The Introduction says microglia’s roles in AD remain unclear and debated, and the section on hiPSC-derived microglia calls for models that preserve interactions with other neural cells. The paper identifies microglia and astrocytes near amyloid-β deposits, but these passages do not establish that interactions with neurons, astrocytes, and plaques specifically are still poorly explored. No page numbers were provided in our copy. (LLM, conf=0.78)

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Cited by

Sorted by citations

Authors
Hemonnot, A.-L., Hua, J., Ulmann, L., & Hirbec, H.
Affiliations
Centre National de la Recherche Scientifique (FR)
Corresponding author
Hirbec, Hélène
ORCID
Venue
Frontiers in Aging Neuroscience
Publisher
Frontiers Media SA
Published
2019-08-30
Volume
11
Pages
233-233
ISSN
1663-4365 (ISSN-L)
DOI
10.3389/fnagi.2019.00233
PMC
PMC6730262
OpenAlex
W2967683178
Cited by
298
References
56
Citations by year
2026: 9 · 2025: 25 · 2024: 34 · 2023: 51 · 2022: 76 · 2021: 59 · 2020: 40 · 2019: 2
FWCI
4.74
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Fondation Plan Alzheimer
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, microglial activation, microglial homeostasis, amyloid deposits, dystrophic neurites, neuroinflammation, microglial function

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