Alzheimer’s β-peptide oligomer formation at physiologic concentrations
Section snippets
Methods and materials
1,1,1,3,3,3-Hexafluoro-2-propanol (HFIP), DMSO, tetramethylbenzidine (free base), N,N-dimethylacetamide, tetrabutylammonium borohydride, and 30% w/w H2O2 were from Sigma–Aldrich (St. Louis, MO). Aβ(1-40) (lot SF1041) and Aβ(1-42) (lot MD0239) were obtained from California Peptide Research (Napa, CA). N-α-biotinyl-Aβ(1-42) (lot 20240) and fluorescein-Aβ(1-42) (lot 21712) were obtained from AnaSpec (San Jose, CA). Fatty-acid-free Fraction V bovine serum albumin (catalog 100377) was from
Results
To study early stages in the formation of multimeric species of human sequence Aβ peptides in vitro and in vivo, a sensitive assay that could determine oligomers in the presence of an excess of monomers was required. Multimeric Aβ(1-42) has been detected by sandwich immunoassay [25], [26], suggesting that the complexes are stable over the time required for their determination by this method. Since concentrations of Aβ peptides in biological fluids range from picomolar to nanomolar [31],
Discussion
Nonfibrillar multimeric species of Aβ peptide are found in biological fluids of AD patients [40], [41]. While the number concentration is low, oligomers apparently harbor much of the toxicity attributed to the Aβ peptide. Oligomers produced in vitro from synthetic β(1-42) peptide mimic the effects of the biological material in several assays [16], [42], [43]. Understanding the early stages of oligomerization in vitro is key to correlating it with the biological process and designing ways to
Acknowledgments
The author gratefully acknowledges helpful discussions with Dr. Mark R. Emmerling, Desiree Watson, Taraneh Haske, and Lori Evans. Thanks also are extended to Dr. Lary Walker for critical reading of the manuscript. Funding was provided by the Sanders–Brown Center on Aging and the Chandler Medical Center of the University of Kentucky.
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