The essential elements of Alzheimer's disease

J Biol Chem. 2021 Jan-Jun:296:100105. doi: 10.1074/jbc.REV120.008207. Epub 2020 Nov 27.

Abstract

Treatments for Alzheimer's disease (AD) directed against the prominent amyloid plaque neuropathology are yet to be proved effective despite many phase 3 clinical trials. There are several other neurochemical abnormalities that occur in the AD brain that warrant renewed emphasis as potential therapeutic targets for this disease. Among those are the elementomic signatures of iron, copper, zinc, and selenium. Here, we review these essential elements of AD for their broad potential to contribute to Alzheimer's pathophysiology, and we also highlight more recent attempts to translate these findings into therapeutics. A reinspection of large bodies of discovery in the AD field, such as this, may inspire new thinking about pathogenesis and therapeutic targets.

Keywords: Alzheimer’s disease; PBT2; clioquinol; copper; ferroptosis; iron; selenium; zinc.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Animals
  • Brain / metabolism
  • Copper / metabolism
  • Ferroptosis
  • Humans
  • Iron / metabolism
  • Phospholipid Hydroperoxide Glutathione Peroxidase / metabolism
  • Plaque, Amyloid / pathology
  • Selenium / metabolism
  • Zinc / metabolism

Substances

  • Copper
  • Iron
  • Phospholipid Hydroperoxide Glutathione Peroxidase
  • Selenium
  • Zinc