Identification of tauopathy-associated lipid signatures in Alzheimer’s disease mouse brain using label-free chemical imaging

• Published in: Communications biology 2024-10, Vol.7 (1), p.1341-11, Article 1341
• Main Authors: Meng, Hao, Elliott, Alicia, Mansfield, Jessica, Bailey, Michelle, Frogley, Mark, Cinque, Gianfelice, Moger, Julian, Stone, Nick, Tamagnini, Francesco, Palombo, Francesca
• Format: Article
• Language: English
• Subjects: 14/19; 14/34; 14/63; 631/57/2282; 692/699/375; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Animals; Biomedical and Life Sciences; Brain - diagnostic imaging; Brain - metabolism; Brain - pathology; Dementia disorders; Disease Models, Animal; Fourier transforms; Hippocampus - diagnostic imaging; Hippocampus - metabolism; Hippocampus - pathology; Life Sciences; Lipid Metabolism; Lipids; Lipids - analysis; Mice; Mice, Transgenic; Microglia; Microscopy; Neurodegenerative diseases; Neuroimaging; Phenotypes; Spectroscopy, Fourier Transform Infrared - methods; Tau protein; Tauopathies - metabolism; Tauopathies - pathology; Transgenic mice
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-07034-3

There is cumulative evidence that lipid metabolism plays a key role in the pathogenesis of various neurodegenerative disorders including Alzheimer’s disease (AD). Visualising lipid content in a non-destructive label-free manner can aid in elucidating the AD phenotypes towards a better understanding of the disease. In this study, we combined multiple optical molecular-specific methods, Fourier transform infrared (FTIR) spectroscopic imaging, synchrotron radiation-infrared (SR-IR) microscopy, Raman and stimulated Raman scattering (SRS) microscopy, and optical-photothermal infrared (O-PTIR) microscopy with multivariate data analysis, to investigate the biochemistry of brain hippocampus in situ using a mouse model of tauopathy (rTg4510). We observed a significant difference in the morphology and lipid content between transgenic (TG) and wild type (WT) samples. Immunohistochemical staining revealed some degree of microglia co-localisation with elevated lipids in the brain. These results provide new evidence of tauopathy-related dysfunction in a preclinical study at a subcellular level. Label-free chemical imaging of ex vivo transgenic mouse brain affected by dementia-inducing tauopathy reveals distinct morphological and biochemical features in a preclinical study.