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 ␤-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. This antibody domain was selected by phage-display from a recombinant library of camelid antibody domains. Surface plasmon resonance, immunoblots, and immunohistochemistry show that this antibody domain distinguishes A␤ amyloid fibrils from disaggregated A␤ peptide as well as from specific A␤ oligomers. The antibody domain possesses functional activity in preventing the formation of mature amyloid fibrils by stabilizing A␤ protofibrils. These data suggest possible applications of B10 in the detection of amyloid fibrils or in the modulation of their formation.neurodegeneration ͉ prion ͉ protein folding

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, A␤2M, AL , and AL 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. By contrast, the early and prefibrillar aggregates formed in an AA amyloidproducing cell system interact with the raft marker ganglioside-1, and amyloid formation is impaired by addition of cholesterolreducing agents. These data suggest the existence of common cellular mechanisms in the generation of different types of clinical amyloid deposits.protein folding ͉ prion ͉ lipid rafts

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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. Compared to normal brain tissue these lipids have an unusual lipid class composition. The most prominent lipid classes were phosphatidylcholine (PC), cholesterol (CH), galactocerebrosides (GC) and sphingomyelin (SM). In addition, the use of micro high-performance liquid chromatography (HPLC) in combination with matrix-assisted laser desorption and ionisation time-of-flight mass spectrometry (MALDI-TOF-MS) allowed the determination of the molecular species of the polar membrane lipid classes present in PHF. The lipid pattern of intracellular PHF shows many characteristics of the conserved lipid pattern previously described for extracellular amyloid fibrils, suggesting similarities in their pathway of formation.