Selective accumulation of aluminum in cerebral arteries in Alzheimer's disease (AD)

J Inorg Biochem. 2013 Sep;126:35-7. doi: 10.1016/j.jinorgbio.2013.05.007. Epub 2013 May 21.

Abstract

Once biologically available aluminum bypasses gastrointestinal and blood-brain barriers, this environmentally-abundant neurotoxin has an exceedingly high affinity for the large pyramidal neurons of the human brain hippocampus. This same anatomical region of the brain is also targeted by the earliest evidence of Alzheimer's disease (AD) neuropathology. The mechanism for the selective targeting and transport of aluminum into the hippocampus of the human brain is not well understood. In an effort to improve our understanding of a pathological aluminum entry system into the brain, this study examined the aluminum content of 8 arteries that supply blood to the hippocampus, including the aorta and several cerebral arteries. In contrast to age-matched controls, in AD patients we found a gradient of increasing aluminum concentration from the aorta to the posterior cerebral artery that supplies blood to the hippocampus. Primary cultures of human brain endothelial cells were found to have an extremely high affinity for aluminum when compared to other types of brain cells. Together, these results suggest for the first time that endothelial cells that line the cerebral vasculature may have biochemical attributes conducive to binding and targeting aluminum to selective anatomical regions of the brain, such as the hippocampus, with potential downstream pro-inflammatory and pathogenic consequences.

Keywords: Aluminum sulfate; Alzheimer's disease; Endothelial cells; Genotoxicity; Human brain microvessel endothelial cells; Inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alum Compounds / toxicity*
  • Aluminum / metabolism*
  • Aluminum / toxicity
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Aorta / drug effects*
  • Aorta / metabolism
  • Aorta / pathology
  • Case-Control Studies
  • Cerebral Arteries / drug effects*
  • Cerebral Arteries / metabolism
  • Cerebral Arteries / pathology
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Hippocampus / blood supply
  • Hippocampus / drug effects*
  • Hippocampus / pathology
  • Humans
  • Ion Transport
  • Middle Aged
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology
  • Primary Cell Culture
  • Spectrophotometry, Atomic

Substances

  • Alum Compounds
  • aluminum sulfate
  • Aluminum