Cholesterol, copper, and accumulation of thioflavine S-reactive Alzheimer’s-like amyloid β in rabbit brain

Accumulation of β-amyloid (Aβ) 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 Aβ in the brain and simultaneous memory deficits, and Aβ accumulation is enhanced if dietary cholesterol is administered. Likewise, dietary cholesterol induces neuronal accumulation of Aβ in New Zealand white rabbits. The cholesterol-induced accumulation of Aβ 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 Aβ in rabbit brain of animals given unaltered distilled water. The numbers of affected neurons and the intensity of neuronal Aβ immunoreactivity is consistently increased among animals administered the copper ion in their drinking water. A copper-induced decrease in the clearance of overproduced Aβ from the brain is proposed as the mechanism causing Aβ accumulation and resulting in the observed memory deficits. Current studies reveal that intensely immunoreactive neurons, extracellular deposits of Aβ, 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 Aβ induced in the brains of rabbits fed a cholesterol diet and administered trace levels of copper ion in their drinking water.