Zinc utilization by microglia in Alzheimer's disease

J Biol Chem. 2024 May;300(5):107306. doi: 10.1016/j.jbc.2024.107306. Epub 2024 Apr 20.


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.

Keywords: Alzheimer’s disease; microglia; neurodegeneration; neuroinflammation; zinc.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease* / metabolism
  • Alzheimer Disease* / pathology
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Humans
  • Microglia* / metabolism
  • Microglia* / pathology
  • Neuroinflammatory Diseases / metabolism
  • Neuroinflammatory Diseases / pathology
  • Zinc* / metabolism
  • tau Proteins / metabolism


  • Zinc
  • Amyloid beta-Peptides
  • tau Proteins