Dementias: the role of magnesium deficiency and an hypothesis concerning the pathogenesis of Alzheimer's disease

Med Hypotheses. 1990 Mar;31(3):211-25. doi: 10.1016/0306-9877(90)90095-v.


Evidence is presented indicating that dementias are associated with a relative insufficiency of Magnesium (Mg) in the brain. Such insufficiency may be attributable to low intake or retention of Mg; high intake of a neurotoxic metal, such as aluminum (Al), which inhibits activity of Mg-requiring enzymes; or impaired transport of Mg and/or enhanced transport of the neurotoxic metal into brain tissue. It is proposed that Alzheimer's disease (AD) involves a defective transport process, characterized by both an abnormally high incorporation of Al and an abnormally low incorporation of Mg into brain neurons. The hypothesis is advanced that an altered serum protein contributes to the progression of AD by having a greater affinity for Al than for Mg, in contrast to the normal protein, which binds Mg better than Al. The altered protein crosses the blood-brain barrier more efficiently than the normal protein and competes with the normal protein in binding to brain neurons. Binding of the altered protein to the target neurons would both facilitate Al uptake and impede Mg uptake. Evidence suggests that albumin is the serum protein that is altered.

MeSH terms

  • Albumins / cerebrospinal fluid
  • Aluminum / poisoning
  • Alzheimer Disease / etiology*
  • Blood Proteins / metabolism
  • Blood-Brain Barrier / physiology
  • Dementia / etiology*
  • Dementia / metabolism
  • Humans
  • Immunoglobulin G / cerebrospinal fluid
  • Magnesium Deficiency / complications*
  • Models, Biological


  • Albumins
  • Blood Proteins
  • Immunoglobulin G
  • Aluminum