β-amyloid is different in normal aging and in Alzheimer disease

Abstract

The mechanism of neurodegeneration caused by β-amyloid in Alzheimer disease is controversial. Neuronal toxicity is exerted mostly by various species of soluble β-amyloid oligomers that differ in their N- and C-terminal domains. However, abundant accumulation of β-amyloid also occurs in the brains of cognitively normal elderly people, in the absence of obvious neuronal dysfunction. We postulated that neuronal toxicity depends on the molecular composition, rather than the amount, of the soluble β-amyloid oligomers. Here we show that soluble β-amyloid aggregates that accumulate in Alzheimer disease are different from those of normal aging in regard to the composition as well as the aggregation and toxicity properties. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.