Figure 6

Toxicity of Aβ wild type and Aβ G37L oligomers (ADDLs) in primary hippocampal cultures. A. SDS-PAGE fractionation of oligomers formed from synthetic Aβ1-42 wild type or G37L. The left panel displays oligomers formed using the "globulomer" preparation of Barghorn et al [21]. The right panel displays oligomers formed using the "ADDL" preparation originally described by Lambert et al [24]. Monoclonal antibody 6E10 recognizes an epitope included in Aβresidues 16-24; mAb NU1 preferentially binds oligomeric Aβ. Note that for both oligomer preparations Aβ G37L tends to form higher molecular weight species. B - D. Representative epifluorescence images of anti-drebrin staining of embryonic rat hippocampal neurons treated after 21 days in culture for 24 hr with vehicle (B), 500 nM Aβ wild type ADDLs (C), or 500 nM Aβ G37L ADDLs (D). Note the strong reduction of drebrin staining is induced by exposure to wild type, but not G37L, ADDLs. E. Hippocampal neurons treated with Aβ G37 ADDLs, washed, fixed, and probed with anti-Aβ oligomer antibody NU1. Note robust binding of the Aβ G37L ADDLs to neurons. F. Quantification of drebrin immunoreactivity in hippocampal neurons exposed to Aβ wild type or G37L ADDLs. Exposure to Aβ wild type ADDLs significantly reduced drebrin immunoreactivity relative to vehicle-treated neurons (*P < 0.01), but no significant reduction was found for Aβ G37L ADDLs or ADDLs formed from a 1:1 mixture of Aβ wild type and G37L (Tukey Multiple Comparisons test).