29 March 2016 Alzheimer's disease imaging biomarkers using small-angle x-ray scattering
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Abstract
There is a need for novel imaging techniques for the earlier detection of Alzheimer's disease (AD). Two hallmarks of AD are amyloid beta () plaques and tau tangles that are formed in the brain. Well-characterized x-ray cross sections of and tau proteins in a variety of structural states could potentially be used as AD biomarkers for small-angle x-ray scattering (SAXS) imaging without the need for injectable probes or contrast agents. First, however, the protein structures must be controlled and measured to determine accurate biomarkers for SAXS imaging. Here we report SAXS measurements of 42 and tau352 in a 50% dimethyl sulfoxide (DMSO) solution in which these proteins are believed to remain monomeric because of the stabilizing interaction of DMSO solution. Our SAXS analysis showed the aggregation of both proteins. In particular, we found that the aggregation of 42 slowly progresses with time in comparison to tau352 that aggregates at a faster rate and reaches a steady-state. Furthermore, the measured signals were compared to the theoretical SAXS profiles of 42 monomer, 42 fibril, and tau352 that were computed from their respective protein data bank structures. We have begun the work to systematically control the structural states of these proteins in vitro using various solvent conditions. Our future work is to utilize the distinct SAXS profiles of various structural states of and tau to build a library of signals of interest for SAXS imaging in brain tissue.
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Mina Choi, Mina Choi, Nadia Alam, Nadia Alam, Eshan Dahal, Eshan Dahal, Bahaa Ghammraoui, Bahaa Ghammraoui, Aldo Badano, Aldo Badano, "Alzheimer's disease imaging biomarkers using small-angle x-ray scattering", Proc. SPIE 9788, Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging, 978802 (29 March 2016); doi: 10.1117/12.2217408; https://doi.org/10.1117/12.2217408
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