Mechanism Noted For Amyloid Aggregation

Aggregates of amyloid β peptides (Aβ) are the main components of plaques that form in the brains of people afflicted with Alzheimer's disease. A new study suggests that one type of Aβ peptide, Aβ40, inhibits the oligomerization of another type, Aβ42 (J. Am. Chem. Soc., DOI: 10.1021/ja8092604). Michael T. Bowers of the University of California, Santa Barbara, and coworkers studied the oligomerization of the two peptides using a combination of ion-mobility spectrometry and mass spectrometry. In a 1:1 mixture, Aβ40 and Aβ42 form single-component and mixed oligomers, the scientists found. Aβ42 forms oligomers as large as dodecamers by stacking planar hexamers, whereas Aβ40 oligomerization stops at tetramers under the conditions of the experiment. But the researchers didn't observe any mixed oligomers larger than tetramers. The findings suggest that Aβ40 "sequesters Aβ42 in stable mixed tetramers, thereby preventing further oligomerization of Aβ42 to form the putative dodecamer toxic agent and consequently potentially deterring the development of [Alzheimer's disease]," the researchers write.