Alzheimer's Disease Research Today is a free monthly online journal that collates and summarizes the latest research about Alzheimer's Disease, including details on diagnosis, memory loss, heredity, treatment, medication.

Alzheimer's disease Abeta peptide fragment 10-30 forms a spectrum of metastable oligomers with marked preference for N to N and C to C monomer termini proximity.

Jablonowska A, Bakun M, Kupniewska-Kozak A, Dadlez M

Department of Biophysics, Institute of Biochemistry and Biophysics, PAS, ul. Pawińskiego 5A, 02-106 Warsaw, Poland.

Oligomers of Abeta peptide have been indicated recently as a possible main causative agent of Alzheimer's disease. However, information concerning their structural properties is very limited. Here Abeta oligomers are studied by non-covalent complexes mass spectrometry and disulfide rearrangement. As a model molecule, an Abeta fragment spanning residues 10-30 (Abeta10-30) has been used. This model peptide is known to contain the core region responsible for Abeta aggregation to fibrils. Non-covalent complexes mass spectrometry indicates that, at neutral pH, monomers are accompanied by oligomers up to hexamers of gradually decreasing population. H-2H exchange studies and direct monomer exchange rate measurements with the use of 15N labeled peptides and mass spectrometry show a fast exchange of monomeric units between oligomers. Disulfide exchange studies of cysteine tagged Abeta10-30 and its mutant show proximity of N-N and C-C termini of monomers in oligomers. The presented data underscore a dynamic character for pre-nucleation forms of Abeta, however, with a marked tendency for parallel strand orientation in oligomers.

Published 16 November 2004 in J Mol Biol, 344(4): 1037-49.
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