Promoting identification of amyotrophic lateral sclerosis based on label‐free plasma spectroscopy

Abstract

Objective: Amyotrophic lateral sclerosis (ALS) is an adult-onset fatal neurodegenerative disease which lacks identified biological markers. A label-free plasma surface-enhanced Raman spectroscopy (SERS) method was developed to explore a simple and noninvasive test for ALS. Methods: ALS patients were enrolled serially and plasma samples were collected at the time of diagnosis prior to the start of ALS treatment. SERS spectra were recorded using a Renishaw micro-Raman system. Results: To exclude the interference by varying disease severity, we enrolled three groups of ALS patients, including ALS-1 (n = 60; ALSFRS-R ≥ 42 and time interval ≤ 12 months), ALS-2 (n = 61; ALSFRS-R < 42 and time interval ≤ 12 months), and ALS-3 (n = 61; ALSFRS-R ≥ 38 and time interval> 12 months). The SERS spectra were analyzed using principal component analysis (PCA), which showed that ALS-1, ALS-2, ALS-3, and control groups were separated significantly. Then, decision tree (DT) models and receiver operating characteristic curves were employed and identified that bands at 722 and 739 cm À1 , and ratios of 635-722 cm À1 and 635-739 cm À1 were able to distinguish ALS from controls significantly. Finally, we highlighted six metabolism pathways correlated with ALS, including phenylalanine-tyrosine-tryptophan biosynthesis, aminoacyl-tRNA biosynthesis, phenylalanine metabolism, pantothenate and CoA biosynthesis, porphyrin and chlorophyll metabolism, and pyrimidine metabolism. Interpretation: Plasma SERS could be a promising tool for the detection of ALS. The bands at 722 and 739 cm À1 , and the ratios of 635-722 cm À1 and 635-739 cm À1 could serve as potential indicator for ALS.

Assessing Causal Relationship Between Human Blood Metabolites and Five Neurodegenerative Diseases With GWAS Summary Statistics

“…Whether phenylalanine has a mediation effect between ALS and MS needs to be further studied. In prior literature, tryptophan and competing neutral amino acid levels were found to be diminished in the plasma of patients with neurodegenerative diseases, the greatest decrease being of tryptophan (Monaco et al, 1979;Zhang et al, 2020). Evidence was also shown that higher serum phenylalanine concentrations related to immune activation are detectable in a subgroup of AD patients (Wissmann et al, 2013).…”

The Emerging Role of Raman Spectroscopy as an Omics Approach for Metabolic Profiling and Biomarker Detection toward Precision Medicine

“…Zhang et al used SERS with PCA and CRT ML algorithm to distinguish Raman spectral data between 182 ALS and 60 healthy patient plasma samples that were mixed with colloidal Ag NPs. 83 The authors identified adenine and coenzyme A (722 cm −1 ), thymine and uracil (739 cm −1 ), and the ratio of tyrosine peak at 635 cm −1 to the aforementioned peaks as the most significant in distinguishing the two cohorts. The SERS bands for nucleic acids were higher in ALS patients confirming well-established literature evidence of altered DNA/RNA metabolism that contribute to genetic mutations in ALS.…”

“…Raman spectral data can then be combined with ML algorithms and multivariate analysis to enable accurate diagnostics of disease progression and discrimination between disease subtypes. By probing these metabolites, RS has characterized tissue, − cells, − and biofluids , including tears, − urine, saliva, − serum, − and plasma. − However, a limitation of spontaneous RS is the time required for a reasonable SNR, which limits both the ability for subcellular imaging and to monitor processes in real time. Both of these characteristics are necessary to understand the mechanistic pathway of metabolic changes.…”

Plasma taurine is an axonal excitability-translatable biomarker for amyotrophic lateral sclerosis

“…We previously reported that the indices of persistent sodium current and fast potassium conductance were significantly associated with survival in ALS patients, and moreover, that a longer strength-duration time constant (SDTC), which indicates an increased persistent sodium current in motor axons, was a strong predictor for ALS survival 7 . Although some metabolites in plasma have been suggested as potential diagnostic/surrogate biomarkers for ALS 8 , no plasma biomarkers closely linked to motor nerve axonal excitability indices specific for ALS have been reported.…”