Utilizing small-angle X-ray microdiffraction to explore neurodegeneration in human brain tissue

TL;DR

This paper explores how X-ray microdiffraction can reveal sub-micrometer voids in brain tissue, which may serve as biomarkers for neurodegeneration in Alzheimer's disease.

Contribution

The study introduces sub-micrometer voids as potential biomarkers for neurodegeneration using X-ray microdiffraction.

Findings

Sub-micrometer voids were detected in fixed, dehydrated brain tissue using X-ray microdiffraction.

The abundance and size of voids correlate with neurodegeneration severity and brain regions affected.

Voids and lesions were mapped across brain regions, complemented by histology and silver-stained images.

Abstract

The power law behavior (I α q-p) seen in the small angle regime of X-ray microdiffraction data from human brain tissue offers a unique opportunity to reveal insights into molecular pathology of disease process in Alzheimer’s disease (AD). The scattering exponent, p, obtained from the slope of log(I)-log(q) plot over a range that extends from 0.007 to 0.1 Å-1 along with uncorrelated SAXS and WAXS intensities revealed, surprisingly, the existence of sub-micrometer sized voids in fixed, dehydrated thin tissue sections. The heterogeneous distribution of voids across the tissue may act as a biomarker to distinguish the regions with significant neurodegeneration.

Using scanning X-ray microdiffraction, we mapped the pathological hallmarks i.e. voids and lesions across brain regions affected by neurodegenerative disease at different stages. The abundance and size of voids were correlated to the regions associated with neurodegeneration and severity of disease. These observations were complemented by silver-stained images and conventional histology providing a novel multi-faceted window for characterizing these neurodegenerative processes. Overall, these interpretations of data across the brain regions involving in the trajectory of disease contribute a better understanding of disease progression.