Researchers at the University of Maryland have developed a new X-ray technique with the FDA that is expected to provide greater insight into Alzheimer’s progression and treatment.
Known as Spectral small-angle X-ray scattering (SAXS), the method is designed to estimate amyloid plaque build-up in the brain.
"Recent studies suggest the presence of amyloid plaques accelerates tau pathology. Therefore, it is worth looking at amyloid plaque amount to detect early AD pathology and understand disease progression. For therapeutics, our method can be used to noninvasively study the effect of disease-modifying treatments that target amyloid-beta aggregation to decrease its load," BIOE alum Eshan Dahal, first author of the paper, told HCB News.
Studying amyloid buildup in Alzheimer’s disease can only be done through postmortem analysis or resource-intensive PET or MR scans that require radiotracer injections. Measuring amyloid amount in vivo is challenging due to the lack of high enough specificity and resolution in images produced.
The authors applied the method to a well-established Alzheimer's disease mouse model with amyloid pathology in just five minutes per studied location in the brain. They did not use any special sample preparation needs or inject contrast agents, but instead relied on SAXS for its ability to identify molecular structures based on scattering patterns. The team created a way to apply a polychromatic X-ray beam and a 2D spectroscopic detector that would enable SAXS to be used on thicker objects, as it mainly is used to assess thin samples.
They found the method was able to effectively and noninvasively detect embedded targets in up to 5 cm-thick objects and in mouse models, and hope the technique can one day be applied to patients whose Alzheimer’s has progressed with an in-office scan that only takes a few minutes.
"It can likely be used to quantify other protein aggregates including tau tangles," said Dahal. "The reason for this is that our method works by capturing X-ray scattering signatures of protein aggregates specific to their nanostructures. We are currently studying methods to differentiate amyloid plaques and tau tangles in the same brain using our X-ray-based method and quantify their amount."
The team plans to pursue human applications soon.
The findings were published in Scientific Reports