Alzheimer’s disease (AD) pathogenesis is widely believed to be associated with the production and deposition of the β-amyloid peptide (Aβ) and neurofibrillary tangles (NFTs) which are composed of a highly-phosphorylated form of the microtubule-associated protein tau. Based on the above hypothesis, there are currently no sufficiently effective technologies and drugs for early detection and treatment of AD. Even the most promising new drug Lecanemab that is based on an anti-amyloid monoclonal antibody therapy, has only partially slowed down the cognitive performance of patients with mild impairment caused by Alzheimer's disease. The main symptoms of AD brain tissue lesions in patients are the deposition of β-amyloid peptide and the hyperphosphorylation of tau protein, which aggregates the microtubule structure of neurons. Therefore, Aβ deposition and hyperphosphorylation of Tau are important pathological biomarkers of Alzheimer's disease. Therefore, the main targets of research for AD prevention, detection and pharmaceuticals are still Aβ and Tau protein. The aim of this study was to detect the changes of Aβ and Tau proteins in the mouse brain tissue with AD and control samples using Visible Resonance Raman (VRR) spectroscopic technology. An attempt was made to develop criteria for the detection of early AD lesions by optical spectroscopy technology. The VRR spectra of AD, the control mouse brain tissues, and Aβ and Tau proteins were recorded and analyzed. The AD and the control mouse brain tissue samples were selected from the thalamus, frontal lobe cortex and hippocampus brain areas. VRR technology with high spatial resolution and the resonance-enhanced features of certain protein molecules is first used in this study to detect and characterize the changes of Aβ and Tau proteins in AD mouse brain model. The optical spectroscopy biomarkers of AD and Control brain tissue were identified in fingerprint and the high-wavenumber regions. The Raman spectra of the secondary structure of protein in amide (I-II-III-B-A) are detected and analyzed. The results indicate that the intensity of Amide I decreased at the 1666 cm-1 corresponding to the β-sheet structure, and the intensity of the amide III bands (1220- 1320 cm-1) increased in all AD brain tissues. It was also observed that the Raman peaks of 1448 and 980 cm-1 related to the abundance of proline, serine, and threonine at tau phosphorylation sites were significantly enhanced in the frontal lobe cortex and hippocampus of AD brain tissues. The intensity ratio biomarker of high phosphorylation in the high wavenumber range from 2898 to 2932 cm-1 increased in all AD brain tissues. Changes of protein secondary conformation and abnormally phosphorylated tau or tauopathies were observed. In summary, VRR is a sensitive tool for characterizing protein structural changes and monitoring the tau phosphorylation. It may potentially be used for early detection of AD.
The unique advantage of visible resonance Raman (VRR) spectroscopy using 532 nm excitation wavelength for biological samples is the resonance enhancement of vibrational modes of chemical bonds from cells and tissues. The aim of this study is specifically to reveal the VRR characteristic spectra of different organs in mice, find the molecular alterations in the development of white matter and gray matter of mouse embryos at different ages and study the VRR spectral information of the mouse embryo head using VRR technology.
The Resonance Raman (RR) spectra of basal cell carcinoma (BCC) and normal human skin tissues were analyzed using 532nm laser excitation. RR spectral differences in vibrational fingerprints revealed skin normal and cancerous states tissues. The standard diagnosis criterion for BCC tissues are created by native RR biomarkers and its changes at peak intensity. The diagnostic algorithms for the classification of BCC and normal were generated based on SVM classifier and PCA statistical method. These statistical methods were used to analyze the RR spectral data collected from skin tissues, yielding a diagnostic sensitivity of 98.7% and specificity of 79% compared with pathological reports.
A clear correlation has been observed between the resonance Raman (RR) spectra of plaques in the aortic tunica intimal wall of a human corpse and three states of plaque evolution: fibrolipid plaques, calcified and ossified plaques, and vulnerable atherosclerotic plaques (VPs). These three states of atherosclerotic plaque lesions demonstrated unique RR molecular fingerprints from key molecules, rendering their spectra unique with respect to one another. The vibrational modes of lipids, cholesterol, carotenoids, tryptophan and heme proteins, the amide I, II, III bands, and methyl/methylene groups from the intrinsic atherosclerotic VPs in tissues were studied. The salient outcome of the investigation was demonstrating the correlation between RR measurements of VPs and the thickness measurements of fibrous caps on VPs using standard histopathology methods, an important metric in evaluating the stability of a VP. The RR results show that VPs undergo a structural change when their caps thin to 66 μm, very close to the 65-μm empirical medical definition of a thin cap fibroatheroma plaque, the most unstable type of VP.
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