Infrared spectral profiling of demyelinating activity in multiple sclerosis brain tissue

Acta Neuropathol Commun. 2024 Sep 10;12(1):146. doi: 10.1186/s40478-024-01854-4.

Abstract

Multiple sclerosis (MS) is a leading cause of non-traumatic disability in young adults. The highly dynamic nature of MS lesions has made them difficult to study using traditional histopathology due to the specificity of current stains. This requires numerous stains to track and study demyelinating activity in MS. Thus, we utilized Fourier transform infrared (FTIR) spectroscopy to generate holistic biomolecular profiles of demyelinating activities in MS brain tissue. Multivariate analysis can differentiate MS tissue from controls. Analysis of the absorbance spectra shows profound reductions of lipids, proteins, and phosphate in white matter lesions. Changes in unsaturated lipids and lipid chain length indicate oxidative damage in MS brain tissue. Altered lipid and protein structures suggest changes in MS membrane structure and organization. Unique carbohydrate signatures are seen in MS tissue compared to controls, indicating altered metabolic activities. Cortical lesions had increased olefinic lipid content and abnormal membrane structure in normal appearing MS cortex compared to controls. Our results suggest that FTIR spectroscopy can further our understanding of lesion evolution and disease mechanisms in MS paving the way towards improved diagnosis, prognosis, and development of novel therapeutics.

Keywords: Biomolecular profiling; Cortex; Demyelinating activity; Fourier transform infrared spectroscopy; Human brain tissue; Lesions; Multiple sclerosis; Sparse partial least squares-discriminant analysis; White matter.

MeSH terms

  • Adult
  • Brain* / metabolism
  • Brain* / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Sclerosis* / metabolism
  • Multiple Sclerosis* / pathology
  • Spectroscopy, Fourier Transform Infrared / methods
  • White Matter / metabolism
  • White Matter / pathology