Feasibility of a label-free X-ray method to estimate brain amyloid load in small animals

Abstract

Background: Amyloid plaque in the brain is associated with a wide range of neurodegenerative diseases such as Alzheimer's and Parkinson's and defined as aggregates of amyloid fibrils rich in β-sheet structures.

New method: We report a label-free method based on small-angle X-ray scattering (SAXS) to estimate amyloid load in an intact mouse head with skull. The method is based on recording and analyzing the X rays elastically scattered from the β-sheets of amyloid plaques in a mouse head at angles smaller than 10° and energies between 30 and 45 keV. The method is demonstrated by acquiring the spectral SAXS data of an amyloid model and an excised head from a wild-type mouse for 600 s.

Results: We captured the distinct scattering peaks of the amyloid plaques at momentum transfer (q) of 6 and 13 nm^-1 associated with β-sheet structure. We first show linear correlation between the mass fraction of the amyloid target and the area under the peak (AUP) of the scattering curve. We report results for estimating amyloid load in a fixed mouse head by recovering the characteristic scattering signal from the amyloid target situated at various locations. The coefficient of variation in the amyloid load estimate is found to be less than 10%.

Comparison with existing methods: There are no previously described label-free X-ray methods for the estimation of amyloid load in an intact head.

Conclusions: We demonstrated the feasibility of a label-free method based on SAXS to potentially estimate brain amyloid in small animals.

Keywords: Alzheimer's disease; Amyloid load estimation; Amyloid plaques; Elastic X-ray scattering; Label-free method; Spectral SAXS.