RAPID INDUCTION OF ALZHEIMER A-BETA AMYLOID FORMATION BY ZINC

A beta(1-40), a major component of Alzheimer's disease cerebral amyloi d, is present in the cerebrospinal fluid and remains relatively solubl e at high concentrations (less than or equal to 3.7 mM). Thus, physiol ogical factors which induce A beta amyloid formation could provide clu es to the pathogenesis of the disease. It has been shown that human A beta specifically and saturably binds zinc. Here, concentrations of zi nc above 300 nM rapidly destabilized human A beta(1-40) solutions, ind ucing tinctorial amyloid formation. However, rat A beta(1-40) binds zi nc less avidly and is immune to these effects, perhaps explaining the scarcity with which these animals form cerebral A beta amyloid. These data suggest a role for cerebral zinc metabolism in the neuropathogene sis of Alzheimer's disease.