Figure 1.

AFM and gel electrophoresis show that toxic ADDL preparations comprise small, fibril-free oligomers of Aβ_1–42. AFM examination of toxic ADDLs shows small globular structures, ≈5–6 nm in size, and a distinct lack of fibrils, consistent with migration of ADDLs as oligomers during gel electrophoresis. (Upper Left) Examination of conventional Aβ preparations by AFM shows primarily large, nondiffusible fibrillar species. (Upper Right) ADDLs imaged by AFM show size and structure consistent with their diffusible nature. (Inset) Native gel of ADDLs made in the cold. Note two major species found at ≈27 and 17 kDa and the absence of large molecular weight species. (Lower Left) Lane W, SDS/PAGE (Western blot) using 6E10 antibody of ADDLs made in the cold. (Lower Right) SDS/PAGE, silver-stained. Lanes: 1, ADDLs made with clusterin; 2, ADDLs made in cold; 3, Centricon 10 retentate of cold-induced ADDLs; 4, Centricon 10 eluate of cold-induced ADDLs. The positions of clusterin monomer, Aβ_1–42, and ADDLs are shown.