FTIR Spectroscopy as a Tool to Address Aβ Impact on Extracellular Vesicles Profile

Alzheimer's disease is a challenge in modern healthcare due to its complex etiology and increasing prevalence. Despite advances, further understanding of Alzheimer's disease pathophysiology is needed, particularly the role of Aβ neurotoxic peptide. Fourier-transform infrared spectroscopy (FTIR) has shown potential as a screening tool for several pathologies, including Alzheimer's disease. Nonetheless, limited research has explored the Aβ direct effects on neurons and extracellular vesicles metabolic profiles. Hence, this study aims to investigate the Aβ impact on the metabolic profiles of a neuronal-like cell line (N2a) and N2a-derived extracellular vesicles, employing FTIR spectroscopy. A comprehensive analysis of spectral data was carried out, focusing on the 1280-900 cm-1 region, including multivariate partial least squares-discriminant analysis (PLS-DA) and peak intensities analysis. PLS-DA analysis revealed moderate to strong correlations within the 1280-900 cm-1 spectral area for both N2a and N2a-derived extracellular vesicles. The peak intensity analysis revealed additional peaks with significant differences in EVs’ spectra relative to N2a following Aβ treatment. Specifically, Aβ seems to cause alterations in protein phosphoryla-tion and in the nucleic acids content of extracellular vesicles. These findings supports that Aβ’s role in Alzheimer's disease pathology may be mediated by extracellular vesicles and highlighting FTIR’s potential for advancing Alzheimer's disease research and clinical applications.