title: Copper excess, zinc deficiency, and cognition loss in Alzheimer's disease.
abstract: In this special issue about biofactors causing cognitive impairment, we present evidence for and discuss two such biofactors. One is excess copper, causing neuronal toxicity. The other is zinc deficiency, causing neuronal damage. We present evidence that Alzheimer's disease (AD) has become an epidemic in developed, but not undeveloped, countries and that the epidemic is a new disease phenomenon, beginning in the early 1900s and exploding in the last 50 years. This leads to the conclusion that something in the developed environment is a major risk factor for AD. We hypothesize that the factor is inorganic copper, leached from the copper plumbing, the use of which coincides with the AD epidemic. We present a web of evidence supporting this hypothesis. Regarding zinc, we have shown that patients with AD are zinc deficient when compared with age-matched controls. Zinc has critical functions in the brain, and lack of zinc can cause neuronal death. A nonblinded study about 20 years ago showed considerable improvement in AD with zinc therapy, and a mouse AD model study also showed significant cognitive benefit from zinc supplementation. In a small blinded study we carried out, post hoc analysis revealed that 6 months of zinc therapy resulted in significant benefit relative to placebo controls in two cognitive measuring systems. These two factors may be linked in that zinc therapy significantly reduced free copper levels. Thus, zinc may act by lowering copper toxicity or by direct benefit on neuronal health, or both.
authors.affiliation: Department of Human Genetics, Medical School University of Michigan, Ann Arbor, MI 48103, USA. brewergj@umich.edu
authors.forename: George J
authors.initials: GJ
authors.lastname: Brewer
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D003300:Copper / Q000378:metabolism*; D006801:Humans; D015032:Zinc / Q000172:deficiency* / Q000378:metabolism
chemical_list: D003300:Copper; D015032:Zinc