Alzheimer’s disease (AD) is the most common type of dementia affecting more than 55 million people worldwide. One of the main pathological features of AD is amyloid plaques, formed by the misfolding of amyloid beta (Aβ) into fibrillar aggregates. While amyloid fibrils have been extensively investigated in-vitro, the exact chemical composition of plaques in the brain and their variations with disease progression is still not fully understood. This underscores the need for studying the chemistry of plaques in AD tissues. Raman spectroscopic imaging is a technique that spatially resolves Raman spectra and thus provides a label-free chemical map of plaques and their microenvironment. However, unequivocal identification amyloid plaques in formalin fixed-paraffin-embedded (FFPE) human brain tissue have not yet been successful. In this study, we use Raman microscopy to investigate the chemical composition of cored Aβ plaques in FFPE tissues and identify the spectral markers for chemical labeling of plaques. We demonstrate that FFPE tissues can be successfully used for studying AD with Raman imaging, and given that FFPE tissue sections are the most common form of archival specimens, these results promise to expand the applications of Raman towards chemical imaging of AD. In addition, we have found the abundance of β-sheets can vary significantly from plaque to plaque. Additionally, our results indicate that Aβ plaques also contain other biomolecules, such as carotenoids, and that ratios between distinctive peaks arising from these biomolecules can be used to characterize these Aβ plaques in FFPE tissues.

Identification of amyloid-beta plaques in formalin-fixed Alzheimer's tissues with Raman microscopy

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.