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

ABSTRACT: INTRODUCTION:Much knowledge about amyloid ? (A?) aggregation and toxicity has been acquired using synthetic peptides and mouse models, whereas less is known about soluble A? 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 A? assembly forms including: (i) monomers, (ii) a ?7 kDa A? 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 A? species. The ?7 kDa A? species resist denaturation by chaotropic agents and have a higher A?42/A?40 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 A? species, the mechanism by which they assemble and the structures they form should reveal therapeutic and diagnostic opportunities.

SUBMITTER: Mc Donald JM 

PROVIDER: S-EPMC4592782 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature