The aqueous phase of Alzheimer's disease brain contains assemblies built from ∼4 and ∼7 kDa Aß species.

INTRODUCTION: Much knowledge about amyloid ß (Aß) aggregation and toxicity has been acquired using synthetic peptides and mouse models, whereas less is known about soluble Aß in human brain. METHODS: We analyzed aqueous extracts from multiple AD brains using an array of techniques. RESULTS: Brains can contain at least four different Aß assembly forms including: (i) monomers, (ii) a ∼7 kDa Aß species, and larger species (iii) from ∼30-150 kDa, and (iv) >160 kDa. High molecular weight species are by far the most prevalent and appear to be built from ∼7 kDa Aß species. The ∼7 kDa Aß species resist denaturation by chaotropic agents and have a higher Aß42/Aß40 ratio than monomers, and are unreactive with antibodies to Asp1 of Ab or APP residues N-terminal of Asp1. DISCUSSION: Further analysis of brain-derived ∼7 kDa Aß species, the mechanism by which they assemble and the structures they form should reveal therapeutic and diagnostic opportunities.