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 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.
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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