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Innate immunity in Alzheimer's disease

Abstract

Alzheimer's disease (AD) is the world's most common dementing illness, affecting over 150 million patients. Classically AD has been viewed as a neurodegenerative disease of the elderly, characterized by the extracellular deposition of misfolded amyloid-β (Aβ) peptide and the intracellular formation of neurofibrillary tangles. Only recently has neuroinflammation emerged as an important component of AD pathology. Experimental, genetic and epidemiological data now indicate a crucial role for activation of the innate immune system as a disease-promoting factor. The sustained formation and deposition of Aβ aggregates causes chronic activation of the immune system and disturbance of microglial clearance functions. Here we review advances in the molecular understanding of the inflammatory response in AD that point to novel therapeutic approaches for the treatment of this devastating disease.

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Figure 1: Clearance of Aβ.

Marina Corral Spence/Nature Publishing Group

Figure 2: Several receptors on microglia contribute to cellular activation by the various forms of Aβ.
Figure 3: Inflammasomes and the production of active IL-1β.

Marina Corral Spence/Nature Publishing Group

Figure 4: External and internal influences on AD.

Marina Corral Spence/Nature Publishing Group

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Acknowledgements

Supported by the Deutsche Forschungsgemeinschaft (Excellence Cluster ImmunoSensation and KFO177 to E.L. and M.T.H.) and by the US National Institutes of Health (1R01HL112661 to E.L.).

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Heneka, M., Golenbock, D. & Latz, E. Innate immunity in Alzheimer's disease. Nat Immunol 16, 229–236 (2015). https://doi.org/10.1038/ni.3102

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