Scanning X-ray microdiffraction studies of protein accumulation and tissue loss in thin sections of human brain tissue in Alzheimer’s disease

Neurodegeneration in Alzheimer's disease is characterized by accumulation of pathological protein deposits including Aβ plaques, tau tangles and diffuse neuropil threads accompanied by wide-spread tissue loss. While dense protein deposits are readily observed by conventional methods, histology struggles to properly capture microscopic evidence of absences corresponding to tissue loss. This study demonstrates the use of scanning X-ray microdiffraction to quantitatively evaluate both protein accumulation and tissue loss in thin sections of human brain tissue across anatomical regions and stages of disease. We show that scanning small-angle microdiffraction can quantify the material properties of tissue through mapping the presence of sub-micron-sized "scattering voids", imaging a tissue attribute that is typically invisible and providing an alternative metric for tissue integrity. Correlation of x-ray data with images of silver-stained sections provided quantitative assessment of protein accumulation readily observed in densely stained features. Regions containing large and abundant scattering voids proved to be highly fragile and closely correspond to locations that were damaged during subsequent tissue processing. This work demonstrates the use of scanning microdiffraction for mapping the abundance of these voids in tissue, providing a detailed description of a phenomena that is typically invisible to histology and utilizing it to study tissue structure across multiple brain regions in diseased human tissue.