Trace metal contamination initiates the apparent auto-aggregation, amyloidosis, and oligomerization of Alzheimer's Abeta peptides.

Nucleation-dependent protein aggregation ("seeding") and amyloid fibril-free formation of soluble SDS-resistant oligomers ("oligomerization") by hydrophobic interaction is an in vitro model thought to propagate beta-amyloid (Abeta) deposition, accumulation, and incur neurotoxicity and synaptotoxicity in Alzheimer's disease (AD), and other amyloid-associated neurodegenerative diseases. However, Abeta is a high-affinity metalloprotein that aggregates in the presence of biometals (zinc, copper, and iron), and neocortical Abeta deposition is abolished by genetic ablation of synaptic zinc in transgenic mice. We now present in vitro evidence that trace ( View Article and Find Full Text PDF