Blood-based molecular signature of Alzheimer's disease via spectroscopy and metabolomics

Habartová, Lucie; Hrubešová, Kateřina; Syslová, Kamila; Vondroušová, Jana; Fišar, Zdeněk; Jirák, Roman; Raboch, Jiří; Setnička, Vladimı́r

doi:10.1016/j.clinbiochem.2019.04.004

Cited by 22 publications

(22 citation statements)

References 46 publications

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“…Our results are in line with the observation that amyloid accumulation in AD brain is associated with an inflammatory process [68][69][70][71][72] , and activated microglia are localized next to (the core of) plaques 28,70,[73][74][75] . Also others reported carotenoid-associated Raman spectra in AD formalin-fixed human brain tissue 76 and in blood plasma 77 which supports the suggestion that the presence of carotenoids may be associated with an ongoing inflammatory process 68 . Carotenoids cannot be synthesized de novo by mammals and therefore must be obtained from diet 78 .…”

Section: Resultssupporting

confidence: 59%

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer’s disease human brain tissue

et al. 2021

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Alzheimer’s disease (AD) neuropathology is characterized by hyperphosphorylated tau containing neurofibrillary tangles and amyloid-beta (Aβ) plaques. Normally these hallmarks are studied by (immuno-) histological techniques requiring chemical pretreatment and indirect labelling. Label-free imaging enables one to visualize normal tissue and pathology in its native form. Therefore, these techniques could contribute to a better understanding of the disease. Here, we present a comprehensive study of high-resolution fluorescence imaging (before and after staining) and spectroscopic modalities (Raman mapping under pre-resonance conditions and stimulated Raman scattering (SRS)) of amyloid deposits in snap-frozen AD human brain tissue. We performed fluorescence and spectroscopic imaging and subsequent thioflavin-S staining of the same tissue slices to provide direct confirmation of plaque location and correlation of spectroscopic biomarkers with plaque morphology; differences were observed between cored and fibrillar plaques. The SRS results showed a protein peak shift towards the β-sheet structure in cored amyloid deposits. In the Raman maps recorded with 532 nm excitation we identified the presence of carotenoids as a unique marker to differentiate between a cored amyloid plaque area versus a non-plaque area without prior knowledge of their location. The observed presence of carotenoids suggests a distinct neuroinflammatory response to misfolded protein accumulations.

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Section: Resultssupporting

confidence: 59%

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer’s disease human brain tissue

et al. 2021

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“…For instance, the predicted rise of patients suffering from Alzheimer’s disease (AD) during the upcoming decades demands a reliable, fast and non-invasive diagnostics method [ 110 ]. Although diagnosing AD becomes more and more based on specific biomarkers, clinical (neuropsychological) assessments combined with magnetic resonance imaging or positron emission tomography are often required for making actual reliable diagnoses [ 111 , 112 , 113 ]. The latter methods are time-consuming, invasive and are unreliable to detect early-stage AD.…”

Section: Application Examplesmentioning

confidence: 99%

“…Averaged ROA spectra of blood plasma patients with Alzheimers disease (red) and non-demented elderly controls (black). Reprinted with permission from ref [113]…”

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confidence: 99%

Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity

et al. 2021

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Chirality plays a crucial role in drug discovery and development. As a result, a significant number of commercially available drugs are structurally dissymmetric and enantiomerically pure. The determination of the exact 3D structure of drug candidates is, consequently, of paramount importance for the pharmaceutical industry in different stages of the discovery pipeline. Traditionally the assignment of the absolute configuration of druggable molecules has been carried out by means of X-ray crystallography. Nevertheless, not all molecules are suitable for single-crystal growing. Additionally, valuable information about the conformational dynamics of drug candidates is lost in the solid state. As an alternative, vibrational optical activity (VOA) methods have emerged as powerful tools to assess the stereochemistry of drug molecules directly in solution. These methods include vibrational circular dichroism (VCD) and Raman optical activity (ROA). Despite their potential, VCD and ROA are still unheard of to many organic and medicinal chemists. Therefore, the present review aims at highlighting the recent use of VOA methods for the assignment of the absolute configuration of chiral small-molecule drugs, as well as for the structural analysis of biologics of pharmaceutical interest. A brief introduction on VCD and ROA theory and the best experimental practices for using these methods will be provided along with selected representative examples over the last five years. As VCD and ROA are commonly used in combination with quantum calculations, some guidelines will also be presented for the reliable simulation of chiroptical spectra. Special attention will be paid to the complementarity of VCD and ROA to unambiguously assess the stereochemical properties of pharmaceuticals.

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“…These techniques allowed for highly accurate discrimination between the study groups via metabolites associated with inflammation, oxidative stress, and lipid metabolism. Finally, SERS analysis of liquid blood has proven to be a targeted, inexpensive, and sensitive diagnostic method [ 109 ]. SERS analysis of blood can be employed in a rapid, nondestructive, and label-free manner to identify information about various analytes.…”

Section: Introductionmentioning

confidence: 99%

Vibrational Spectroscopy for Identification of Metabolites in Biologic Samples

et al. 2020

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Vibrational spectroscopy (mid-infrared (IR) and Raman) and its fingerprinting capabilities offer rapid, high-throughput, and non-destructive analysis of a wide range of sample types producing a characteristic chemical “fingerprint” with a unique signature profile. Nuclear magnetic resonance (NMR) spectroscopy and an array of mass spectrometry (MS) techniques provide selectivity and specificity for screening metabolites, but demand costly instrumentation, complex sample pretreatment, are labor-intensive, require well-trained technicians to operate the instrumentation, and are less amenable for implementation in clinics. The potential for vibration spectroscopy techniques to be brought to the bedside gives hope for huge cost savings and potential revolutionary advances in diagnostics in the clinic. We discuss the utilization of current vibrational spectroscopy methodologies on biologic samples as an avenue towards rapid cost saving diagnostics.

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Blood-based molecular signature of Alzheimer's disease via spectroscopy and metabolomics

Cited by 22 publications

References 46 publications

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer’s disease human brain tissue

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer’s disease human brain tissue

Tackling Stereochemistry in Drug Molecules with Vibrational Optical Activity

Vibrational Spectroscopy for Identification of Metabolites in Biologic Samples

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