Targeting Alzheimer’s disease - studying the fibril structure of the Amyloid beta protein on a laboratory system
The fibril structure of Amyloid beta has been studied with the SAXSpoint 2.0 system.
Amyloid beta is a protein that is closely linked to Alzheimer's disease (AD) and the Down syndrome. Its function in the body and the potential triggering of AD is still poorly understood and a topic of major research. The currently most commonly accepted theory for the development of Alzheimer's disease involves the formation of amyloid fibrils in the brain tissue (plaque). The amyloid proteins can form soluble oligomers which can fold to different structures. Current research suggest that misfolded oligomers can induce a misfolding of other amyloid fibrils, leading to a chain reaction resulting in the formation of plaques. These plaques are believed to be toxic to nerve cells.
Understanding the formation of these fibrils is one of the key aspects in preventing the outbreak of Alzheimer's disease. The amyloid fibril and oligomers can be studied with X-ray scattering methods to get an insight into their folding behavior in an controlled environment, e. g. at a specific pH or the presence of certain trigger molecules. Using external forces (e. g., electric fields) the fibrils can also be aligned and become anisotropic.1 Due to the design of the instrument and its experimental flexibility, the SAXSpoint 2.0 is the ideal tool to carry out such measurements.
Experimental and Results
The samples were measured using the SAXSpoint 2.0 instrument in combination with the PasteCell and the TCStage 150. A slurry of amyloid beta fibrils was prepared in buffer solution and kindly provided by Vanessa Morris (TU Munich), Christoph Göbl (University of Toronto), and Tobias Madl (Medical University of Graz). A small amount of this slurry was transferred into the PasteCell, the sample temperature was kept constant at 4 °C.
Fig. 1 2D diffraction pattern of the Amyloid beta fibrils
Fig. 2 Diffraction pattern of Amyloid beta fibrils
The diffraction pattern of the amyloid fibrils is displayed in Figure 2. The indicated reflections at 6.2 nm-1 and 13.4 nm-1 can be assigned to the distance of the both beta-sheets (at 10 Å) and the interstrand spacing (at 4.7 Å).1 This opens up insight in understanding how the aggregation works and how to possible prevent the formation of plaques.
1 Sunde, M., Serpell, L. C., Bartlam, M., Fraser, P. E., Pepys, M. B., & Blake, C. C. (1997). Common core structure of amyloid fibrils by synchrotron X-ray diffraction. Journal of Molecular biology, 273(3), 729-739.