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Microglia Activation and Anti-inflammatory Regulation in Alzheimer’s Disease

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Abstract

Inflammatory regulators, including endogenous anti-inflammatory systems, can down-regulate inflammation thus providing negative feedback. Chronic inflammation can result from imbalance between levels of inflammatory mediators and regulators during immune responses. As a consequence, there are heightened inflammatory responses and irreversible tissue damage associated with many age-related chronic diseases. Alzheimer’s disease (AD) brain is marked by prominent inflammatory features, in which microglial activation is the driving force for the elaboration of an inflammatory cascade. How the regulation of inflammation loses its effectiveness during AD pathogenesis remains largely unclear. In this article, we will first review current knowledge of microglial activation and its association with AD pathology. We then discuss four examples of anti-inflammatory systems that could play a role in regulating microglial activation: CD200/CD200 receptor, vitamin D receptor, peroxisome proliferator-activated receptors, and soluble receptor for advanced glycation end products. Through this, we hope to illustrate the diverse aspects of inflammatory regulatory systems in brain and neurodegenerative diseases such as AD. We also propose the importance of neuronal defense systems, because they are part of the integral inflammatory and anti-inflammatory systems. Augmenting the anti-inflammatory defenses of neurons can be included in the strategy for restoration of balanced immune responses during aging and neurodegenerative diseases.

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Acknowledgements

We thank the following supports: NINDS (RO1 NS049075 to LFL) and Alzheimer’s Association (IIRG-09-91996 to LFL; IIRG-06-26125 to DGW). We are grateful to the Banner Sun Health Research Institute Brain Donation Program of Sun City, Arizona for the provision of human biological materials for the study of human cells and postmortem tissues. The Brain Donation Program is supported by the National Institute on Aging (P30 AG19610 Arizona Alzheimer’s Disease Core Center), the Arizona Department of Health Services (contract 211002, Arizona Alzheimer’s Research Center), the Arizona Biomedical Research Commission (contracts 4001, 0011, 05-901 and 1001 to the Arizona Parkinson’s Disease Consortium) and the Prescott Family Initiative of the Michael J. Fox Foundation for Parkinson’s Research.

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Authors and Affiliations

  1. Laboratory of Neuroregeneration, Banner Sun Health Research Institute, 10515 West Santa Fe Drive, Sun City, AZ, 85351, USA

    Lih-Fen Lue

  2. Department of Cell Biology and Anatomy, National Cheng Kung University Medical College, Tainan, Taiwan

    Yu-Min Kuo

  3. Civin Laboratory of Neuropathology, Sun City, AZ, USA

    Thomas Beach

  4. Laboratory of Neuroinflammation, Banner Sun Health Research Institute, Sun City, AZ, USA

    Douglas G. Walker

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  1. Lih-Fen Lue
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  2. Yu-Min Kuo
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Correspondence to Lih-Fen Lue.

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Lue, LF., Kuo, YM., Beach, T. et al. Microglia Activation and Anti-inflammatory Regulation in Alzheimer’s Disease. Mol Neurobiol 41, 115–128 (2010). https://doi.org/10.1007/s12035-010-8106-8

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