Alzheimer's disease imaging biomarkers using small-angle x-ray scattering

Mina Choi; Nadia Alam; Eshan Dahal; Bahaa Ghammraoui; Aldo Badano

doi:10.1117/12.2217408

29 March 2016 Alzheimer's disease imaging biomarkers using small-angle x-ray scattering

Mina Choi, Nadia Alam, Eshan Dahal, Bahaa Ghammraoui, Aldo Badano

Proceedings Volume 9788, Medical Imaging 2016: Biomedical Applications in Molecular, Structural, and Functional Imaging; 978802 (2016) https://doi.org/10.1117/12.2217408
Event: SPIE Medical Imaging, 2016, San Diego, California, United States

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 (Aβ) plaques and tau tangles that are formed in the brain. Well-characterized x-ray cross sections of Aβ 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 Aβ₄₂ 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 Aβ₄₂ 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 Aβ₄₂ monomer, Aβ₄₂ 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 Aβ and tau to build a library of signals of interest for SAXS imaging in brain tissue.

Citation Download Citation

Mina Choi, Nadia Alam, Eshan Dahal, Bahaa Ghammraoui, and 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); https://doi.org/10.1117/12.2217408

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