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Updated: Mar 22, 2026
Cell-based Assay to Study Antibody-mediated Tau Clearance by Microglia
Published on: November 9, 2018
Targeting microglia for the treatment of Alzheimer's Disease
Paul D Wes1, Faten A Sayed2, Frédérique Bard3
1Neuroinflammation Department, Lundbeck Research USA, Paramus, New Jersey.
Abstract:
While histological changes in microglia have long been recognized as a pathological feature of Alzheimer's disease (AD), recent genetic association studies have also strongly implicated microglia in the etiology of the disease. Coding and noncoding polymorphisms in several genes expressed in microglia-including APOE, TREM2, CD33, GRN, and IL1RAP-alter AD risk, and therefore could be considered as entry points for therapeutic intervention. Furthermore, microglia may have a substantial effect on current amyloid β (Aβ) and tau immunotherapy approaches, since they are the primary cell type in the brain to mediate Fc receptor-facilitated antibody effector function. In this review, we discuss the considerations in selecting microglial therapeutic targets from the perspective of drug discovery feasibility, and consider the role of microglia in ongoing immunotherapy clinical strategies. GLIA 2016;64:1710-1732.
Insights
Microglia play a key role in Alzheimer's disease (AD) pathogenesis and immunotherapy. Targeting microglial genes offers potential therapeutic strategies for AD drug discovery and treatment.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Microglia, the brain's immune cells, are increasingly recognized for their significant role in Alzheimer's disease (AD) etiology.
- Genetic studies highlight microglial genes (e.g., APOE, TREM2, CD33) as critical factors influencing AD risk.
Purpose of the Study:
- To review therapeutic target selection for microglia in drug discovery for Alzheimer's disease.
- To discuss the influence of microglia on current amyloid-beta and tau immunotherapy strategies.
Main Methods:
- Review of genetic association studies implicating microglial genes in AD risk.
- Analysis of microglial function in Fc receptor-mediated antibody effector mechanisms.
- Consideration of drug discovery feasibility for microglial targets.
Main Results:
- Polymorphisms in microglial genes (APOE, TREM2, CD33, GRN, IL1RAP) are associated with altered AD risk.
- Microglia are crucial mediators of antibody-based immunotherapy for AD.
- Drug discovery must consider microglial biology for effective therapeutic interventions.
Conclusions:
- Microglia represent promising targets for novel Alzheimer's disease therapeutics.
- Understanding microglial roles is essential for optimizing current and future AD immunotherapies.
- Feasible drug discovery strategies should focus on microglial pathways to combat AD.
