Different Effect of Vitamin D₂ and Vitamin D₃ on Amyloid-β40 Aggregation In Vitro

Title:Different Effect of Vitamin D₂ and Vitamin D₃ on Amyloid-β40 Aggregation In Vitro

Volume: 11 Issue: 8

Author(s): Midori Suenaga, Hironobu Takahashi, Hiroshi Imagawa, Michiru Wagatsuma, Shinji Ouma, Yoshio Tsuboi, Akiko Furuta and Yoichi Matsunaga

Affiliation:

Keywords: Aggregation, Alzheimer's disease, amyloid-β, β-sheet formation, quartz-crystal microbalance technique, vitamin D derivatives.

Abstract: The seeding of amyloid-β 40 (Aβ40) oligomers from monomers is the initial step of Aβ aggregation, and many reports have suggested that cholesterol enhances this step. We studied the potential of secosteroid vitamin D derivatives for Aβ40 aggregation in vitro. The quartz-crystal microbalance technique demonstrated that vitamin D₃ does not show any effect on Aβ40 aggregation while vitamin D₂ promoted it and docking simulation but that vitamin D₂ has high potential in this regard. Thus, stacking of the Phe19 benzene ring in Aβ40 and the C22-C23 double bond in vitamin D₂ may alter the energy of these molecules. Electron microscopy revealed the potential of vitamin D₂ to increase Aβ40 aggregation. Thioflavin-T assays indicated that Vitamin D₂ induced increased fluorescence at 490 nm, as typically observed for amyloid fibrils but also for protofibrils; in both cases this reflects of the increase of β-sheet contents. Aβ40 aggregation was further confirmed in ELISA, SDS-PAGE and dot blot analysis which revealed changes in protease K resistance. These results suggest a possible mechanism, of how vitamin D₂ could increase Aβ40 aggregation and the docking simulation explains, why the same is not observed with vitamin D₃.

Cite this article as:

Suenaga Midori, Takahashi Hironobu, Imagawa Hiroshi, Wagatsuma Michiru, Ouma Shinji, Tsuboi Yoshio, Furuta Akiko and Matsunaga Yoichi, Different Effect of Vitamin D₂ and Vitamin D₃ on Amyloid-β40 Aggregation In Vitro, Current Alzheimer Research 2014; 11 (8) . https://dx.doi.org/10.2174/156720501108140910121139