Rapid induction of Alzheimer A beta amyloid formation by zinc

Aβ1-40, a major component of Alzheimer's disease cerebral amyloid, is present in the cerebrospinal fluid and remains relatively soluble at high concentrations (less than or equal to 3.7 mM). Thus, physiological factors which induce Aβ amyloid formation could provide clues to the pathogenesis of the disease. It has been shown that human Aβ specifically and saturably binds zinc. Here, concentrations of zinc above 300 nM rapidly destabilized human Aβ1-40 solutions, inducing tinctorial amyloid formation. However, rat Aβ1-40 binds zinc less avidly and is immune to these effects, perhaps explaining the scarcity with which these animals form cerebral Aβ amyloid. These data suggest a role for cerebral zinc metabolism in the neuropathogenesis of Alzheimer's disease.