Raman spectroscopic identification of biochemical alterations in Alzheimer's disease brain tissue.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by chronic inflammation, neuronal loss, and continuous decline in memory and cognitive function. Raman Spectroscopy (RS) offers a powerful, label‑free approach for detecting early biochemical alterations in AD by generating highly sensitive molecular fingerprints, which is valuable for identifying subtle changes associated with protein misfolding, lipid dysregulation, and oxidative stress, key processes underlying AD onset and progression. In our study, full‑spectrum RS revealed clear biochemical distinctions between control and AD brain tissues, as well as between Braak IV and Braak VI AD stages. Multivariate analytical methods, including Singular Value Decomposition (SVD) and Linear Discriminant Analysis (LDA), were applied to manage spectral complexity and highlight the principal biochemical contributors to AD pathology. Multiple Raman bands in the 1200-1800 cm-1 region showed increased intensity in AD tissue, including 1296 cm-1 (lipid CH₂ deformation), 1440 cm-1 (lipid/cholesterol deformation), 1554 cm-1 (Amide II), 1585 cm-1 (protein‑folding-related vibrations), and 1640-1680 cm-1 (Amide I). These changes indicate enhanced protein aggregation, loss of ordered secondary structure, and extensive lipid membrane disorganization. Complementary gene‑expression analysis further demonstrated dysregulation of lipid homeostasis in AD, with altered expression of ABCA1, LIPE, CPT1A, PPARA, and SREBP‑1, indicating broad metabolic reprogramming. Together, the coordinated spectral and transcriptional shifts underscore lipid‑metabolic dysfunction as a central feature of AD. By capturing these molecular signatures, RS provides a promising tool for early detection and monitoring of AD progression.

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