Tear-based vibrational spectroscopy for noninvasive biomarker discovery in amyotrophic lateral sclerosis.
Duse A., Ambrosio F., Ami D., Borghesi A., Cozza F., Grandori R., Lunetta C., Natalello A., Pezzoli F., Ponzini E., Tavazzi S., Zeri F.
Biofluid analysis by vibrational spectroscopies is gaining interest due to its potential to revolutionize diagnostics and precision medicine. However, the lack of robust biomarkers combined with the unaccomplished identification of convenient biofluids has drastically hampered optical advancements in clinical diagnosis and monitoring of neurodegenerative disorders. Our findings show that vibrational spectroscopy is a new potential amyotrophic lateral sclerosis (ALS) diagnostic approach and indicate that tears are a reliable and non-invasive source of ALS biomarkers. Our proposed approach has been validated using Fourier transform infrared (FTIR) and Raman microspectroscopies. In conjunction with multivariate analysis, this vibrational approach made it possible to discriminate between tears from ALS patients and healthy controls (HCs) with high specificity ($97%$ and $100%$ for FTIR and Raman spectroscopy, respectively) and sensitivity ($88%$ and $100%$ for FTIR and Raman spectroscopy, respectively). Additionally, this work allowed us to disclose ALS spectroscopic markers related to protein and lipid alterations, as well as to a reduction of the phenylalanine level, in comparison with HCs.