Structural characterization of a soluble amyloid beta-peptide oligomer - PubMed (original) (raw)

. 2009 Mar 10;48(9):1870-7.

doi: 10.1021/bi802046n.

Rohinton Edalji, John E Harlan, Thomas F Holzman, Ana Pereda Lopez, Boris Labkovsky, Heinz Hillen, Stefan Barghorn, Ulrich Ebert, Paul L Richardson, Laura Miesbauer, Larry Solomon, Diane Bartley, Karl Walter, Robert W Johnson, Philip J Hajduk, Edward T Olejniczak

Affiliations

Structural characterization of a soluble amyloid beta-peptide oligomer

Liping Yu et al. Biochemistry. 2009.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder that is linked to the presence of amyloid beta-peptides that can form insoluble fibrils or soluble oligomeric assemblies. Soluble forms are present in the brains and tissues of Alzheimer's patients, and their presence correlates with disease progression. Long-lived soluble forms can be generated in vitro by using small amounts of aliphatic hydrocarbon chains of detergents or fatty acids in preparations of amyloid beta-peptides. Using NMR, we have characterized soluble oligomers of Abeta preglobulomer and globulomer that are stable and alter synaptic activity. The NMR data indicate that these soluble forms have a mixed parallel and antiparallel beta-sheet structure that is different from fibrils which contain only parallel beta-sheets. Using the structural data, we engineered a disulfide bond into the soluble Abeta globulomer to give a "new" soluble antigen that is stable, homogeneous, and binds with the same affinity to selective antibodies as the parent wt globulomer.

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