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A state of delirium: deciphering the effect of inflammation on tau pathology in Alzheimer's disease

Barron, Matthew; Gartlon, Jane; Dawson, Lee A.; Atkinson, Peter J.; Pardon, Marie-Christine

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Authors

Matthew Barron

Jane Gartlon

Lee A. Dawson

Peter J. Atkinson



Abstract

Alzheimer's disease (AD), the predominant form of dementia, is highly correlated with the abnormal hyperphosphorylation and aggregation of tau. Immune responses are key drivers of AD and how they contribute to tau pathology in human disease remains largely unknown. This review summarises current knowledge on the association between inflammatory processes and tau pathology. While, preclinical evidence suggests that inflammation can indeed induce tau hyperphosphorylation at both pre- and post-tangles epitopes, a better understanding of whether this develops into advanced pathological features such as neurofibrillary tangles is needed. Microglial cells, the immune phagocytes in the central nervous system, appear to play a key role in regulating tau pathology, but the underlying mechanisms are not fully understood. Their activation can be detrimental via the secretion of pro-inflammatory mediators, particularly interleukin-1?, but also potentially beneficial through phagocytosis of extracellular toxic tau oligomers. Nevertheless, anti-inflammatory treatments in animal models were found protective, but whether or not they affect microglial phagocytosis of tau species is unknown. However, one major challenge to our understanding of the role of inflammation in the progression of tau pathology is the preclinical models used to address this question. They mostly rely on the use of septic doses of lipopolysaccharide that do not reflect the inflammatory conditions experienced AD patients, questioning whether the impact of inflammation on tau pathology in these models is dose-dependent and relevant to the human disease. The use of more translational models of inflammation corroborated with verification in clinical investigations are necessary to progress our understanding of the interplay between inflammation and tau pathology.

Citation

Barron, M., Gartlon, J., Dawson, L. A., Atkinson, P. J., & Pardon, M. (2017). A state of delirium: deciphering the effect of inflammation on tau pathology in Alzheimer's disease. Experimental Gerontology, 94, 103-107. https://doi.org/10.1016/j.exger.2016.12.006

Journal Article Type Article
Acceptance Date Dec 7, 2016
Online Publication Date Dec 12, 2016
Publication Date Aug 30, 2017
Deposit Date Jan 17, 2017
Publicly Available Date Mar 29, 2024
Journal Experimental Gerontology
Print ISSN 0531-5565
Electronic ISSN 1873-6815
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 94
Pages 103-107
DOI https://doi.org/10.1016/j.exger.2016.12.006
Keywords Alzheimer's disease; Tau; Phosphorylation; Inflammation; Preclinical models; Lipopolysaccharide
Public URL https://nottingham-repository.worktribe.com/output/835519
Publisher URL https://www.sciencedirect.com/science/article/pii/S0531556516305800

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