Colocalization of β-Sheets and Carotenoids in Aβ Plaques Revealed with Multimodal Spatially Resolved Vibrational Spectroscopy.

The aggregation of amyloid β(Aβ) peptides is at the heart of Alzheimer's disease development and progression. As a result, amyloid aggregates have been studied extensively in vitro, and detailed structural information on fibrillar amyloid aggregates is available. However, forwarding these structural models to amyloid plaques in the human brain is still a major challenge. The chemistry of amyloid plaques, particularly in terms of the protein secondary structure and associated chemical moieties, remains poorly understood. In this report, we use Raman microspectroscopy to identify the presence of carotenoids in amyloid plaques and demonstrate that the abundance of carotenoids is correlated with the overall protein secondary structure of plaques, specifically to the population of β-sheets. While the association of carotenoids with plaques has been previously identified, their correlation with the β structure has never been identified. To further validate these findings, we have used optical photothermal infrared (O-PTIR) spectroscopy, which is a spatially resolved technique that yields complementary infrared contrast to Raman. O-PTIR unequivocally demonstrates the presence of elevated β-sheets in carotenoid-containing plaques and the lack of β structure in noncarotenoid plaques. Our findings underscore the potential link between anti-inflammatory species as carotenoids to specific secondary structural motifs within Aβ plaques and highlight the possible role of chemically distinct plaques in neuroinflammation, which can uncover new mechanistic insights and lead to new therapeutic strategies for AD.