The Journal of biological chemistryApr 22, 2024

How brain immune cells use zinc in Alzheimer's disease

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Zinc dyshomeostasis is implicated in Alzheimer's disease pathogenesis.

Alzheimer's disease is characterized by amyloid-β plaques and neurofibrillary tangles.
Microglia play a dual role in Alzheimer's, providing both neuroprotection and potential neurotoxicity.
Nutrient and trace metal utilization by microglia is crucial for their activation and function.
Zinc is essential for brain health and may influence neuroinflammation in Alzheimer's disease.
Understanding zinc's role could inform new therapeutic strategies for treating Alzheimer's disease.

Simplified

Alzheimer's disease (AD) is the most common form of dementia defined by two key pathological characteristics in the brain, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Microglia, the primary innate immune cells of the central nervous system (CNS), provide neuroprotection through Aβ and tau clearance but may also be neurotoxic by promoting neuroinflammation to exacerbate Aβ and tau pathogenesis in AD. Recent studies have demonstrated the importance of microglial utilization of nutrients and trace metals in controlling their activation and effector functions. Trace metals, such as zinc, have essential roles in brain health and immunity, and zinc dyshomeostasis has been implicated in AD pathogenesis. As a result of these advances, the mechanisms by which zinc homeostasis influences microglial-mediated neuroinflammation in AD is a topic of continuing interest since new strategies to treat AD are needed. Here, we review the roles of zinc in AD, including zinc activation of microglia, the associated neuroinflammatory response, and the application of these findings in new therapeutic strategies.

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Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.

PubMed

How brain immune cells use zinc in Alzheimer's disease

Abstract

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