Abstract
Biofluid analysis by optical spectroscopy techniques is attracting considerable interest due to its potential to revolutionize diagnostics and precision medicine, particularly for neurodegenerative diseases. However, the lack of effective biomarkers combined with the unaccomplished identification of convenient biofluids has drastically hampered optical advancements in clinical diagnosis and monitoring of neurodegenerative disorders. Here, we show that vibrational spectroscopy applied to human tears opens a new route, offering a non-invasive, label-free identification of a devastating disease such as amyotrophic lateral sclerosis (ALS). Our proposed approach has been validated using two widespread techniques, namely, 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, the investigation of tears 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. Our findings show that vibrational spectroscopy is a new potential ALS diagnostic approach and indicate that tears are a reliable and non-invasive source of ALS biomarkers.
Highlights
Amyotrophic lateral sclerosis (ALS) is one of the most severe neurodegenerative disorders characterized by degeneration of upper and lower motor neurons, leading to death in a median time of 3 years from onset
Sixty-three patients with definite and probable ALS according to the revised El Escorial Criteria[27] and 46 healthy controls (HCs) subjects were enrolled (Table S1)
After the deposition on the IR transparent BaF2 support and excess water evaporation, tears displayed a typical fern-like morphology (Figures S1 and S3), surrounded by an amorphous drop border, called coffee ring, which was excluded from Fourier transform infrared (FTIR) analysis, being its IR absorption intensity too high to obtain reliable results, while measurable by Raman spectroscopy
Summary
Amyotrophic lateral sclerosis (ALS) is one of the most severe neurodegenerative disorders characterized by degeneration of upper and lower motor neurons, leading to death in a median time of 3 years from onset. The diagnosis of ALS is achieved by the combination of clinical data and neurophysiological evidence of motor neuron degeneration, together with symptom progression, leading to a delay between onset and diagnosis that limits prompt intervention. The use of a microscope allows collecting the signal from a selected sample area with a spatial resolution that depends on the instrument characteristics. This property makes this approach suitable for the Received: June 17, 2021 Accepted: December 2, 2021 Published: December 14, 2021
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