Abeta-globulomers are formed independently of the fibril pathway.

Soluble A beta-oligomers are currently discussed as the major causative species for the development of Alzheimer's disease (AD). Consequently, the beta-amyloid cascade hypothesis was extended by A beta-oligomers and their central neuropathogenic role in AD. However, the molecular structure of A beta-oligomers and their relation to amyloid fibril formation remains elusive.

Directed selection of a conformational antibody domain that prevents mature amyloid fibril formation by stabilizing Abeta protofibrils.

The formation of amyloid fibrils is a common biochemical characteristic that occurs in Alzheimer's disease and several other amyloidoses. The unifying structural feature of amyloid fibrils is their specific type of beta-sheet conformation that differentiates these fibrils from the products of normal protein folding reactions. Here we describe the generation of an antibody domain, termed B10, that recognizes an amyloid-specific and conformationally defined epitope.

Identification of molecular compounds critical to Alzheimer's-like plaque formation.

Amyloid diseases are characterized by the formation of insoluble amyloid fibrils from previously soluble polypeptides. In Alzheimer's disease (AD), amyloid fibrils, formed from beta-amyloid peptides, are deposited as extracellular amyloid plaques only inside the brain. As previously shown, Alzheimer's-like plaque formation in human monocyte culture recapitulates the features of in vivo amyloid plaque formation.

Paired helical filaments contain small amounts of cholesterol, phosphatidylcholine and sphingolipids.

By using qualitative and quantitative high-performance thin layer chromatography (hpTLC) we found lipids associated with purified Alzheimer's (AD) paired helical filaments (PHF) in an amount of 1.4+/-0.2% of the total anhydrous mass.

Alzheimer-like plaque formation by human macrophages is reduced by fibrillation inhibitors and lovastatin.

The cerebral deposition of Abeta-peptide as amyloid fibrils and plaques represents a hallmark characteristic of Alzheimer's disease (AD). AD plaques are defined by their green birefringence after Congo red staining, their spherulite-like superstructure and their association with specific secondary components. Here we show that primary human macrophages promote the formation of amyloid plaques that correspond in all aforementioned characteristics to typical amyloid plaques from diseased tissues: they consist of aggregated Abeta-peptide, they reveal the typical ''Maltese cross" structure and they are associated with the secondary components glycosaminoglycanes, apolipoprotein E (apoE) and the raft lipids cholesterol and sphingomyelin.

Raft lipids as common components of human extracellular amyloid fibrils.

Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis of amyloid fibrils derived from various human diseases (AA, ATTR, Abeta2M, ALlambda, and ALkappa amyloidosis) shows that these are associated with a common lipid component that has a conserved chemical composition and that is specifically rich in cholesterol and sphingolipids, the major components of cellular lipid rafts. This pattern is not notably affected by the purification procedure, and no tight lipid interactions can be detected when preformed fibrils are mixed with lipids.