Raman spectroscopic signatures of amyloid fibrils: Insights into structural and biochemical changes in human tissues

Abstract

Amyloid fibrils, characterized by β-sheet-rich protein aggregates, are closely associated with various diseases. Understanding the structural and biochemical changes in amyloid formation requires detailed characterization of their Raman spectroscopic signatures. This study evaluated the application of Raman spectroscopy, utilizing a 532-nm laser excitation source, for differentiating amyloid from normal tissues. Raman spectroscopy effectively identifies protein secondary structures and distinguishes normal tissues from amyloid-containing tissues, offering potential for real-time diagnosis. A total of 13 amyloid tissue samples (heart, kidney, and thyroid) and 9 normal controls were analyzed. Key spectral differences were observed in the amide I (∼1660 cm⁻¹) and amide III (∼1300 cm⁻¹) regions, characteristic of β-sheet structures in amyloid fibrils. Spatially resolved Raman spectra revealed molecular heterogeneity between amide and lipid components in amyloid deposits. Ratiometric analysis further supported this, demonstrating significant differences in the amide-to-lipid ratio (with attributed significant peak intensities at 1660 cm⁻¹ for amide I and 1440 cm⁻¹ for lipids) between amyloid and control tissues. Statistical analysis (Mann-Whitney U test, p = 0.006) confirmed significant differences in amide group intensities between amyloid and control tissues. These findings highlight Raman spectroscopy as a promising tool for real-time identification and characterization of amyloid deposits, with potential clinical applications in diagnosing amyloid-related diseases.