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Multitasking Microglia and Alzheimer’s Disease: Diversity, Tools and Therapeutic Targets

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Abstract

Given the importance of microglia to inflammatory, phagocytic and synaptic modulatory processes, their function is vital in physiological and pathological brain. The impairment of microglia in Alzheimer’s disease has been demonstrated on genetic, epigenetic, transcriptional and functional levels using unbiased systems level approaches. Recent studies have highlighted the immense phenotypic diversity of microglia, including the ability to adopt distinct and dynamic phenotypes in ageing and disease. We review the origins and functions of healthy microglia and the established and emerging models and techniques available for their study. Furthermore, we highlight recent advances on the role, heterogeneity and dysfunction of microglia in Alzheimer’s disease and discuss the potential for therapeutic interventions targeting microglia. Microglia-selective molecular fingerprints will guide detailed functional analysis of microglial subsets and may aid in the development of therapies specifically targeting microglia.

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Acknowledgments

AG is funded by the NHMRC-ARC Dementia Development Research Fellowship. KMK and TM are funded by the Academy of Finland Fellowship and Emil Aaltonen foundation.

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Authors and Affiliations

  1. Department of Pathology, University of Melbourne, Parkville, Australia

    Alexandra Grubman

  2. Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia

    Alexandra Grubman

  3. The Florey Institute of Neuroscience and Mental Health, Parkville, Australia

    Alexandra Grubman

  4. Department of Neurobiology, A.I.Virtanen Institute for Molecular Sciences, The University of Eastern Finland, Kuopio, Finland

    Katja M Kanninen & Tarja Malm

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  1. Alexandra Grubman
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  2. Katja M Kanninen
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  3. Tarja Malm
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Correspondence to Alexandra Grubman.

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Grubman, A., Kanninen, K.M. & Malm, T. Multitasking Microglia and Alzheimer’s Disease: Diversity, Tools and Therapeutic Targets. J Mol Neurosci 60, 390–404 (2016). https://doi.org/10.1007/s12031-016-0825-5

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