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ToolsRivers-Auty, Jack, Tapia, Victor S., White, Claire S., Daniels, Michael J. D., Drinkall, Samuel, Kennedy, Paul T., Spence, Harry G., Yu, Shi, Green, Jack P, Hoyle, Christopher, Cook, James, Bradley, Amy, Mather, Alison E., Peters, Ruth, Tzeng, Te-Chen, Gordon, Margaret J., Beattie, John H., Brough, David and Lawrence, Catherine B. (2021) Zinc status alters Alzheimer’s disease progression through NLRP3-dependent inflammation. The Journal of Neuroscience, 41 (13). pp. 3025-3038. ISSN 0270-6474
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Abstract
Alzheimer’s disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer’s disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer’s disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer’s disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer’s disease fed a control (35mg/kg zinc) or diet deficient in zinc (3mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer’s-like memory deficits without modifying amyloid beta (β) plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer’s disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ps1,alzheimer's disease,inflammation,microglia,nlrp3,zinc,neuroscience(all) ,/dk/atira/pure/subjectarea/asjc/2800 |
| Faculty \ School: | |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 05 Mar 2021 00:44 |
| Last Modified: | 06 Jun 2024 15:14 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/79375 |
| DOI: | 10.1523/JNEUROSCI.1980-20.2020 |
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