Mechanisms of Hybrid Oligomer Formation in the Pathogenesis of Combined Alzheimer's and Parkinson's Diseases
Figure 6
Electron microscopy analysis of hybrid oligomers and fibrils of Aβ and α-syn.
In vitro cell-free preparations of vehicle, Aβ alone, α-syn alone, or Aβ and α-syn were incubated for 6 hrs or 48 hrs and prepared for electron microscopy analysis. (A–D) After 6 hrs of incubation, compared to vehicle alone (A), Aβ (B) and α-syn (C) alone formed globular structures of 5–10 nm in diameter, while incubation of Aβ and α-syn together (D) resulted in the formation of larger, well-defined ring-like structures with a central channel. (E) Analysis of numbers of ring-like structures formed after 6 hrs incubation. (F–I) After 48 hrs of incubation, compared to vehicle alone (F), Aβ (G) and α-syn (H) alone or in combination (I) formed fibrils of about 11 nm in diameter. (J–M) After 6 hrs incubation in the presence of lipid monolayers, compared to vehicle alone (J), Aβ (K) and α-syn (L) alone formed globular structures of 5–8 nm in diameter, while incubation of Aβ and α-syn together (M) resulted in enhanced formation of larger, well-defined, ring-like structures. Scale bar, 10 nm (A–D, J–M); 100 nm (F–I).