Copper and Alzheimer's Disease

Adv Neurobiol. 2017:18:199-216. doi: 10.1007/978-3-319-60189-2_10.


Alzheimer's disease (AD) is the most common form of adult neurode-generation and is characterised by progressive loss of cognitive function leading to death. The neuropathological hallmarks include extracellular amyloid plaque accumulation in affected regions of the brain, formation of intraneuronal neurofibrillary tangles, chronic neuroinflammation, oxidative stress, and abnormal biometal homeostasis. Of the latter, major changes in copper (Cu) levels and localisation have been identified in AD brain, with accumulation of Cu in amyloid deposits, together with deficiency of Cu in some brain regions. The amyloid precursor protein (APP) and the amyloid beta (Aβ) peptide both have Cu binding sites, and interaction with Cu can lead to potentially neurotoxic outcomes through generation of reactive oxygen species. In addition, AD patients have systemic changes to Cu metabolism, and altered Cu may also affect neuroinflammatory outcomes in AD. Although we still have much to learn about Cu homeostasis in AD patients and its role in disease aetiopathology, therapeutic approaches for regulating Cu levels and interactions with Cu-binding proteins in the brain are currently being developed. This review will examine how Cu is associated with pathological changes in the AD brain and how these may be targeted for therapeutic intervention.

Keywords: Alzheimer’s disease; Amyloid precursor protein; Ceruloplasmin; Clioquinol; Copper; Neuroinflammation; PBT-2; Reactive oxygen species; Tau.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / metabolism*
  • Brain / metabolism*
  • Brain / pathology
  • Copper / metabolism*
  • Humans
  • Inflammation
  • Oxidative Stress
  • Plaque, Amyloid / metabolism*
  • Plaque, Amyloid / pathology
  • Reactive Oxygen Species / metabolism


  • APP protein, human
  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Reactive Oxygen Species
  • Copper