Surface-enhanced raman spectroscopy as a biomarker for Huntington’s disease

<h3>Background</h3> The lack of a blood biomarker hampers progress in Huntington’s Disease (HD). We investigated the use of Surface-Enhanced Raman Spectroscopy (SERS) on human serum as a potential biomarker. <h3>Methods</h3> Serum samples (94 patients and 38 controls) were collected from patients and controls attending a multidisciplinary HD clinic in Cambridge. 5µl serum was mixed with 5µl gold Nanoparticles and 1µl 10x PBS, allowed to aggregate for 45 minutes, then exposed to a focused 785nm laser in a Raman microscope. Resultant emission spectra were recorded, then pre-processed and analysed against clinical measures recorded at the sample visit. <h3>Results</h3> Using Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) on processed spectra, we were able to separate premanifest and manifest HD patients from controls. We also found a relationship between disease measures (such as the motor components of Unified Huntington’s Disease Rating Scale or the number of CAG repeats) and serum spectral regions in gene-carriers. We also conducted exploratory longitudinal analysis on patient disease trajectories using this data. <h3>Conclusions</h3> The spectral profile of human serum acquired by SERS demonstrates potential as a possible biomarker for HD but further validation and and optimisation is needed in larger, longer longitudinal studies.