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Targeting innate immunity to protect and cure Alzheimer’s disease: opportunities and pitfalls

Abstract

Innate immunity has been the focus of many new directions to understand the mechanisms involved in the aetiology of brain diseases, especially Alzheimer’s disease (AD). AD is a multifactorial disorder, with the innate immune response and neuroinflammation at the forefront of the pathology. Thus, microglial cells along with peripheral circulating monocytes and more generally the innate immune response have been the target of several pre-clinical and clinical studies. More than a decade ago, inhibiting innate immune cells was considered to be the critical angle for preventing and treating brain diseases. After the failing of numerous clinical trials and the discovery that it may actually be the opposite in various pre-clinical models, the field has changed considerably. Here, we present both sides of the story with a particular emphasis on the beneficial properties of innate immune cells and how they can be targeted to have neuroprotective properties.

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Fig. 1: Summary of different strategies to modulate innate immune response.
Fig. 2: Boosting microglia proliferation enhance remyelination.
Fig. 3: Targeting the peripheral immune system.

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Acknowledgements

This work was supported by the Canadian Institutes in Health Research (CIHR) foundation grant and les Fonds de recherche du Québec- Santé (FRQS) via the research center funding grant. GC was supported by CIHR postdoctoral fellowship, while SR was supported by a CIHR Canada Research Chair in Neuroimmunology.

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Cisbani, G., Rivest, S. Targeting innate immunity to protect and cure Alzheimer’s disease: opportunities and pitfalls. Mol Psychiatry (2021). https://doi.org/10.1038/s41380-021-01083-4

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