Small-angle X-ray scattering characterization of a β -amyloid model in phantoms

Abstract

Objective: We present a method to prepare an amyloid model at scalable quantities for phantom studies to evaluate small-angle x-ray scattering systems for amyloid detection. Two amyloid models were made from a plasma protein with and without heating. Both models mimic the $\beta$-sheet structure of the $\beta$-amyloid ($\beta \text{A}$) plaques in Alzheimer's disease. Amyloid detection is based on the distinct peaks in the scattering signature of the $\beta$-sheet structure. We characterized the amyloid models using a spectral small-angle x-ray scattering (sSAXS) prototype with samples in a plastic syringe and within a cylindrical polymethyl methacrylate (PMMA) phantom.

Results: sSAXS data show that we can detect the scattering peaks characteristic of amyloid $\beta$-sheet structure in both models around 6 and 13 ${\text{nm}}^{-1}$. The $\beta \text{A}$ model prepared without heating provides a stronger signal in the PMMA phantom. The methods described can be used to prepare models in sufficiently large quantities and used in samples with different packing density to assess the performance of $\beta \text{A}$ quantification systems.

Keywords: Alzheimer’s disease; Amyloid; SAXS.

Fig. 1

Model preparation and experimental setup. a Schematic of $\beta \text{A}$ model preparation, heated (left) and unheated (right). b Syringe sample of an amyloid model. c sSAXS system setup. d Dimensions of the cylindrical PMMA phantom

Fig. 2

Characterization of the heated and unheated $\beta \text{A}$ models in a syringe. a Scattering signal of the heated model using 600 and 1800 s data acquisition times. b Effect of BSA concentration in the scattering signal of the heated model. Error bar represents standard deviations from $\text{n}=3$ measurements. c Scattering signal of the unheated model for 600 and 1800 s from $\text{n}=2$ measurements. d Representative 2D detector data of the unheated model in 30 to 45 keV energy range

Fig. 3

Characterization of the unheated $\beta \text{A}$ model in a cylindrical PMMA phantom. a–c 2D detector data before and after background subtraction. d Scattering signal from the PMMA phantom with and without the unheated $\beta \text{A}$ model. e Recovered scattering peaks associated with amyloids after background subtraction. Error bar represents standard deviations from n = 3 measurements