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.