Cholesterol, copper, and accumulation of thioflavine S-reactive Alzheimer's-like amyloid beta in rabbit brain.

Abstract

Accumulation of beta-amyloid (Abeta) in the Alzheimer's disease (AD) brain is considered to be causally related to the behavioral symptoms of the disorder. Transgenic mouse models of AD exhibit accumulation of Abeta in the brain and simultaneous memory deficits, and Abeta accumulation is enhanced if dietary cholesterol is administered. Likewise, dietary cholesterol induces neuronal accumulation of Abeta in New Zealand white rabbits. The cholesterol-induced accumulation of Abeta in rabbit brain is increased when distilled drinking water is supplemented with 0.12 ppm copper ion (as copper sulfate) compared to the cholesterol-induced accumulation of Abeta in rabbit brain of animals given unaltered distilled water. The numbers of affected neurons and the intensity of neuronal Abeta immunoreactivity is consistently increased among animals administered the copper ion in their drinking water. A copper-induced decrease in the clearance of overproduced Abeta from the brain is proposed as the mechanism causing Abeta accumulation and resulting in the observed memory deficits. Current studies reveal that intensely immunoreactive neurons, extracellular deposits of Abeta, and brain vessels in cholesterol-fed rabbits given copper-supplemented water were stained by thioflavine S. Thioflavine S-reactive features were not observed in cholesterol-fed rabbits given unaltered distilled drinking water. The data suggest that there is an accumulation of fibrillar Abeta induced in the brains of rabbits fed a cholesterol diet and administered trace levels of copper ion in their drinking water.