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Review
. 2019 Aug 30:11:233.
doi: 10.3389/fnagi.2019.00233. eCollection 2019.

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

Anne-Laure Hemonnot  1 , Jennifer Hua  1 , Lauriane Ulmann  1 , Hélène Hirbec  1
Affiliations
Review

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

Anne-Laure Hemonnot et al. Front Aging Neurosci. .

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.

Keywords: Alzheimer disease; early stage; hiPSCs; microglia; microglia diversity; neuroinflammation; purinergic signaling; sexual dimorphism.

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Figures

FIGURE 1
FIGURE 1
Schematic representation of functions microglial cells can loose and gain in context of AD. Microglia is represented in green associated to amyloid-β deposit in purple and dendritic spines in gray.
FIGURE 2
FIGURE 2
Schematic representation of the current hot topics and emerging microglial targets in AD physiopathology studied in this review. Microglia is represented in green and either with a reactive shape associated to amyloid-β deposit in purple or in the parenchyma with an homeostatic shape, away from Aβ.
See this image and copyright information in PMC

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