Serum Raman spectroscopy as a diagnostic tool in patients with Huntington's disease

Abstract

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by an abnormal CAG expansion in exon 1 of the huntingtin (HTT) gene. Given its genetic basis it is possible to study patients both in the pre-manifest and manifest stages of the condition. While disease onset can be modelled using CAG repeat size, there are no easily accessible biomarkers that can objectively track disease progression. Here, we employed a holistic approach using spectral profiles generated using both surface-enhanced Raman spectroscopy (SERS) and Raman Spectroscopy (RS), on the serum of healthy participants and HD patients covering a wide spectrum of disease stages. We found that there was both genotype-and gender-specific segregation on using the full range in the fingerprint region with both SERS and RS. On a more detailed interrogation using specific spectral intervals, SERS revealed significant correlations with disease progression, in particular progression from pre-manifest through to advanced HD was associated with serum molecules related to protein misfolding and nucleotide catabolism. Thus, this study shows the potential of Raman spectroscopy-based techniques for stratification of patients and, of SERS, in particular, to track disease status through provision of 'spectral' biomarkers in HD, with clinical applications for other diseases and trials looking at disease modifying therapies.

Identification of amyloid beta in small extracellular vesicles via Raman spectroscopy

“…In the research field of neurological disorders, Raman spectroscopy has been used to investigate structural features and changes of toxic proteins such as Aβ [47][48][49] , α-synuclein 50,51 , and tau 52 by analyzing the amide bands in the protein spectrum that is particularly sensitive to the protein's conformational state and environment. Moreover, differences in the Raman fingerprint of blood samples of patients compared to a healthy control have been reported for a variety of neurological conditions such as AD 53 , Parkinson's disease (PD) 54,55 , dementia with Lewy bodies 56 , and Huntington disease 57 . Recent reports have demonstrated the ability of Raman spectroscopy to accurately distinguish PD 58 and Amyotrophic Lateral Sclerosis (ALS) 59 patients from healthy control group based on their EVs profile.…”

“…Moreover, differences in the Raman fingerprint of blood samples of patients compared to a healthy control have been reported for a variety of neurological conditions such as AD, 53 Parkinson's disease (PD), 54,55 dementia with Lewy bodies, 56 and Huntington disease. 57 Recent reports have demonstrated the ability of Raman spectroscopy to accurately distinguish PD 58 and Amyotrophic Lateral Sclerosis (ALS) 59 patients from healthy control group based on their EVs profile. Our group previously demonstrated the application of laser tweezers Raman spectroscopy for exosomes heterogeneity analysis 39 and surface-enhanced Raman spectroscopy for biochemical analysis of EVs.…”

Random Lasing Detection of Mutant Huntingtin Expression in Cells

“…In a recent paper, Huefner et al [ 34 ] successfully conducted Raman spectroscopy for the diagnosis of HD by observing differences in the analysis of the Raman signals of blood serum in patients with or without the disease. They applied a multivariate statistical analysis with PCA–LDA to examine their spectroscopic data.…”

“…In particular, the first two components (PC1 and PC2) accounted for over 67% of the variability. Interestingly, some studies have suggested that PCA per se may be enough to distinguish between different biological samples [ 34 , 36 ].…”

Human red blood cell behaviour in hydroxyethyl starch: probed by single cell spectroscopy

“…Recently Barker et al have demonstrated the potential of Raman spectroscopy as a promising tool for monitoring the biochemical features of Huntington's disease and its progression by studying blood serum. 2 Similar reports have also appeared in the Lancet this year, recommending the use of Raman spectroscopy as a cost effective tool for identifying colorectal cancer (CRC) which can reduce colonoscopies and the other diagnostic requirements for patients in the Urgent Suspected Cancer (USC) pathway for CRC. 3 Raman spectroscopy based blood tests have also provided better performance as compared to the conventional USC pathway for cancer prediction.…”