Alzheimer’s disease (AD) is characterized by the presence of extracellular deposits of amyloid-beta peptides (known as AD plaques). Its assessment is usually achieved post-mortem, requiring chemical pre-treatment via an antibody or indirect labelling. Label-free imaging techniques, like auto-fluorescence, spontaneous Raman (SpR) and stimulated Raman (SRS) imaging could be performed on tissue in its native state to study the biomolecular composition of AD plaques and contribute to a better understanding of the disease. Here we present imaging results of human brain amyloid core plaques. We show blue and green autofluorescence emission localized at the same plaque position while Raman spectroscopy revealed the presence of carotenoids at the same spot. For identifying the underlying carotenoids, first carotenoid reference spectra in hexane solution and then adsorbed on aggregated Aβ42 peptides were recorded. From the six carotenoids measured, lycopene matched closest with the Raman peak positions observed in the measured AD plaque. Furthermore, we used SRS to investigate the presence of a lipid halo around plaque locations as reported in literature for transgenic AD mice.
Current publications show promising results in the in-vivo detection of amyloid deposits in the retina of Alzheimer’s disease (AD) patients as well in post-mortem flat mounted retinal tissue. The results are promising for the detection of early alterations associated with AD. The aim of our study was to confirm recently published findings using almost identical methodology, blue (ex: λ = 486 nm) fluorescence retinal imaging, curcumin as labelling fluorophore, and a similar data analyzing process.
The use of a single multimode fiber (MMF) as a high-resolution endoscopic imaging tool is
demonstrated. We show that the scrambled output of a MMF can be used for auto-fluorescence
compressive imaging. By scanning a light spot across the proximal side of the fiber we can create
uncorrelated speckle patterns at the output. Those patterns successively illuminate the biological
sample and for each pattern the integrated intensity is recorded in epi-direction. An image of the brain
tissue was computationally reconstructed using a regularization algorithm. Furthermore, the
presented technique has potential in enhanced acquisition speed and in improving the resolution limit.
The retina might be a promising target to identify early alterations associated with Alzheimer’s Disease (AD). Recent publications show promising results in the detection of retinal amyloid in AD patients in-vivo as well in post-mortem retinal tissue. The aim of this study is to confirm previously published findings using fluorescent retinal imaging and curcumin as labelling fluorophore.
In total, 40 patients were enrolled (26 AD, 14 controls) and the subjects’ amyloid assessment was based on CSF analysis and/or amyloid PET. We administered three different curcumin formulations: Longvida, Theracurmin and Novasol. Blue fluorescence (λ = 486 nm) retinal baseline and follow-up images of 2 to 6 retinal regions were performed.
The resulting images were visually assessed in a multidisciplinary setting and a selection of images were quantitatively analyzed (only from participants receiving Longvida and Novasol). The visual analysis of baseline images showed no increased fluorescence in AD patients compared to controls. Furthermore, no difference was found comparing pre- and post-curcumin images within AD and control patients. The quantitatively analysis confirmed the visual analysis, identifying similar amount of fluorescence spots in AD and control patients, even after curcumin intake.
Despite previous studies assessing retinal amyloid in AD patients with fluorescent retinal imaging using curcumin, we could not confirm the retinal changes described in previous studies. We were unable to reproduce the discrimination of AD patients from controls based on fluorescent retinal amyloid visualization.
Label-free imaging of Alzheimer’s disease (AD) brain tissue could contribute to a better understanding of its pathology. Here, we present a comprehensive study of sequentially applied spectroscopic and imaging modalities on snap-frozen AD tissue.
Alzheimer’s disease (AD) is the most common form of dementia, which is one of the main death leading causes with around 46 million people affected worldwide. Alzheimer’s disease is characterized by the accumulation of extracellular deposits of proteins in the brain, known as amyloid-beta (Aβ) plaques. Currently, in-vivo detection of Aβ pathology is solely possible by two invasive techniques: the analysis of cerebral fluid or PET imaging. Raman spectroscopy may be an alternative way of in-vivo diagnosis of Aβ deposits as it is sensitive to concentrations of biomolecules. It is an established and common non-destructive technique, which in addition allows for minimal sample preparation. Recent publications on transgenic mouse and human AD brain tissue suggest that Raman spectroscopy is an adequate technique to identify and localize Aβ plaques1,2. However, publications on human tissue lack the proof of plaque existence at the same location, imaged with Raman spectroscopy. The present study is designed to confirm ultimately a match between Raman spectra and possible amyloid-beta plaque locations. This is achieved by superimposing the autofluorescence image, the Raman imaging map and the stained fluorescence image of the same tissue section. Additionally, obtained data will be compared to previous studies of post mortem human AD brain tissue that was formalin fixed and paraffin embedded.
Dementia is one of the main death leading causes worldwide and Alzheimer’s disease (AD) is its most common form. In postmortem examinations of AD brain tissue, extracellular deposits of proteins are observed, known as amyloid-beta (Aß) plaques. Aß plaques are characterized by their occurrence of beta-sheets and are, beside tau tangles, biological hallmarks in the postmortem diagnosis of AD. Little research on the detectability of Aß deposits in brain tissue using Raman spectroscopy has been published.
Here, we examined formalin fixed, paraffin embedded tissue slices of AD and healthy control cases. The slices have been spectrally raster imaged with a step size smaller the size of a plaque using a commercial Raman spectroscope with a NIR laser source to obtain a hyperspectral map of the size of 0.5mm2. Specific band intensities including, among others, protein and lipid components were analyzed and afterward compared to the healthy control cases to study spectral differences. Further, Aß deposit locations could be precisely matched to the obtained spectral data by staining the same Raman imaged tissue slice with Thioflavin afterward. In addition, plaques can be co-localized by using histochemical stained adjacent tissue slices.
In conclusion, we present new insights on spectral changes in the Raman fingerprint region of 950 to 1800cm-1 when analyzing the molecular composition of AD brain tissue.
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